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The Value of the Tuberculin Skin Test as a Screening Test for Tuberculosis among BCG-Vaccinated Children

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“In \I((iicine one must pay attention not to piausii)le theorizing but to experience and reason togetiler. . . . I agree that theorizing is to be approved, provided that it is based on facts, and systematically makes its (le(iuctions from what is observed. . . . But conclusions drawn from

tlnai(i(’d reason can hardly he serviceable; only those drawil from observed fact.” hippocrates:

PreC(’/)tS.

. . .

(Short (O711UZUH1C(ltU)7lS of factual material arc published here. Comments (111(1 (ritici.sms appear

(is Letters to the L(litOr.)

624

Experience

and Reason

. .

Briefly

Recorded

: ‘#{149}

The Value

of the Tuberculin

Skin Test

as a Screening

Test for

Tuberculosis

among

BCG-Vaccinated

Children

A major objection raised against the use of

BCG-vaccination is tilat it negates the

useful-ness of the tuberculin skin test as a screening

procedure for tuberculosis infection.4 This consideratioll has deterred a great many mdi-viduals and organizations fronl use of the ‘ac-cine despite impressive evidence of its value. Furtiler, in individual cases, tilis concept results

in a failure to skill test the vaccinated child or a

imsunderstandmg of the significance of a

posi-tive test. It is the purpose of this paper to

describe a set of conditions under which the

tuberculin test can continue as a useful

screen-ing procedure for tuberculosis in a BCG-vac-cillated ppul1t)11.

Three cases of primary pulmonary

tubercu-losis in BCG-vaccinated children are presented. These cllildren had all been vaccinated as

new-0 All tilree cases were discovered by

routin(’ tuberculin testing. Tile following study

was tilen undertaken to determine what con-stitutes a significantly positive tuberculin

re-action in this group of BCG-vaceinated chil-dren.

Case 1

CASE REPORTS

P. \V., a Navajo female, was born at Fort

Dc-fiance Indian llosl)itai. At 48 hours of age she was vaccinated with BC(;.

She was then well until age 3 ears, when she

0 Rosenthal strain, Ivophilized, BCG vaccine

ad-Ill inistere(l b niultipuncture disk.

was admitted to FDIII with viral gastroentenitis

and stonlatitis. Routine PPD, intermediate strength,

was negative. Recovery was uneventful.

At age 7 she entered school and a routine

tuber-culin te’t was positive. Roentgenogram revealed

linear scarring in the right upper lobe and

calci-fications in the right hilus. Physical exanlination

was normal. WBC was normal; ESR, 26. Skin test

%Vitil 5 tuberculin units

(

TU

)

of PPD resulted in

15 111111 induration. Skin tests with histoplasmosis,

coccidionivcosis, and blastomycosis antigens were

negative. Sile was felt to have calcified primary

tuberculosis.

Case 2

N!. Y., a Navajo female born at FDIH, was

vac-cinated on day 5 of life.

When the patient was 4 years old her father was

discovered to have active pulmonary tuberculosis. The child reacted to 5 TU of PPD with 12 mm

induration. There was no history of prior

tuber-culin tests.

She was asymptonlatic and physical examination was nornlal. WBC was normal; ESR, 18.

Roent-genogran showed left hilar adenopathy and a

linear infiltrate adjacent to the left heart border.

Skin tests for histoplasmosis, coccidionlycosis and

biastomycosis were negative. She was treated with isoniazid. Roentgenogram one year later revealed

a left pleuropenicardial adhesion and calcifications

in the left hiltis.

Case 3

E. S., a Navajo female, was vaccinated with

BCG on the third day of life.

She was tilen well until 1 year of age when she

developed a right middle lobe pneumonia.

Inter-mediate strength PPD was negative. She was

treated with penicillin and made an uneventful

recovery, with cOlllplete clearing of the

roentgeno-gram .3 weeks later.

(2)

EXPERIENCE AND REASON-BRIEFLY RECORDED 625

At 13 years of age she developed measles. Two

days after the original fever cleared it recurred,

along with a worsening cough and generalized rales.

A right upper lobe infiltrate was present on

roent-genogranu and she was admitted to FDIH.

Tuber-cuiin test with 5 TU of PPD resulted in 20 mm

induration. She was treated with INH and PAS as

well as penicillin. Gastric washings were negative

for acid fast organisms.

Six months later roentgenogram revealed an en-larged left hilus and residual infiltrate in the right

upper lobe. At 23 years of age the child was well

and treatment discontinued. Follow-up at age 4

revealed calcifications in both right and left hilus.

MATERIALS AND METHODS

Fort Defiance Indian Hospital is a United States Public Health Service Hospital on the Navajo Reservation in Arizona. The reservation itself covers 24,000 square miles, with a thinly spread population of 90,000. Conditions over most of the reservation are still primitive. Most of the population still live in isolated “camps,” extended family groups, ranging in size from 5 to 50 persons. Despite increasing use of frame houses, the single room “hogan” of logs and mud remains the typical dwelling. Transporta-tion is a major problem; many roads are

im-passable in bad weather.

Despite improvements in case finding and treatment, tuberculosis remains an important problem. In 1961, the incidence of tuberculosis among Indians was 7.5 times the national

aver-age, and the death rate 4 times greater.#{176} In

1963, tuberculosis accounted for 4% of the

pediatric admissions to FDIH. Many adults

re-main undiagnosed or refuse treatment. Mcdi-cine men and “singers” are often consulted in-stead of physicians. The hot, dry climate is ideal for the evaporation of droplets to a size

small enough to penetrate to the alveolus, and

the small crowded hogan is ideal for the spread of these droplets.

It is noteworthy that despite these factors,

the incidence of positive skin tests among in-fants and preschool children is still low enough

for the test to remain useful. Over most of the

reservation less than 5% of school beginners

are tuberculin positive. This is probably due chiefly to the lack of urbanization on the

neser-vation. Public health measures are also

impor-tant including, paradoxically, the use of BCC. Infants born at FDIH receive BCG while in the newborn nursery. “Rosenthal strain” vac-cine, obtained in lyophilized form from the Research Foundation and Institute of

Tubercu-positive

skin tests

l00

90

80

70

60

50

40

30

20

I0

. i . 3 . 4 5 6

age I, years

Foe. 1. Percentage of reactors

(

5 mm and over

)

to

100 TU of PPD.

losis Research, Chicago, is used immediately after reconstitution. One drop (50 mg/rnl) is administered to the deltoid region by multiple puncture with a disk having 36 points. Two hundred and fifty children thus vaccinated

were tuberculin tested at 6 weeks to 6 years

of age. They were consecutive patients as seen

by the author in both ward and clinic, with the

following exclusions: moribund children, chil-dren who had had measles or measles vaccine

in the preceding 60 days, and children on

ster-oids. Each child was tested with 5 and 100 TU

of PPD, with disposable tuberculin syringes and needles. Test material was refrigerated and used within 48 hours of dilution. All tests were

administered and read by the author, generally

at 48 hours, a few at 72 hours. The maximum

diameter of the indurated area was measured

and recorded.

RESULTS

Figure 1 shows the percentage positive re-actors to 100 TU of PPD. The percentage falls

off rapidly between 3 and 12 months, but is

reasonably stable thereafter at approximately

50%.

Figure 2 illustrates the percentage reactors to 5 TU of PPD. In this graph 5 mm induration is taken as positive, thereby including weak

(

5-9 mm) as well as strong (10 mm and over)

reactors.

Figure 3 is the critical graph. It represents

the percentage strong reactors (10 mm and

over) to 5 TU of PPD. This percentage falls off

6 Alternately supplied by Merck, Sharp, and

(3)

I’

age in years

626

/. positive

skin tests

$00

90 80

70

60

50 40

30

20

I0

FIG. 2. Percentage of reactors

(

5 mm and over

)

to

5 TU of PPD.

rapidly from a high of 31% at S months to zero at 9 months.

COMMENT

Many authors agree that the tuberculin

sensitivity following BCC is less pronounced than after a natural infection, and that it tends

to decrease with increasing time after vaccina-tiofl.10, Aronson and Taylorl2 state that tu-berculin sensitivity after BCG is generally low,

with only a small percentage reacting to

smaller amounts of OT or PPD.

Many factors are involved in determining tuberculin sensitivity after BCG and recorded

studies vary from 8% to 97%.’ Some of the

more important variables may be mentioned

briefly. BCG vaccines from different sources

vary, both in potency and in uniformity.1 The

concentration of vaccine used, as well as the dose, may vary from study to study. There are differences in the mode of storage and trans-portation, and tile vital question of fresh versus

freeze-dried preparations. This aspect of the problem, the heterogenicity of BCG, has been adequately reviewed by Willis and

Vandi-5 Vandi-5 The vaccine may be given by

intra-dermai injection or by multiple puncture with a needle or a disk with a varying number of points. Age at the time of vaccination is most important. There is evidence, both expenimen-tally and li10 that newborns develop less skin sensitivity after BCG than do older subjects.

The chief materials used for skin testing

today are OT and PPD. Aronson and Taylorul

found that more BCG-vaccinated children ne-acted to OT than PPD in equal doses.

Birk-.,. positive ski, tests

00

90

80

70

60

50 40

30

20

I0

I

age in years

FIG. 3. Percentage of strong reactors ( 10 mm and

over) to 5 TU of PPD.

haug1 found 30% less reactors to PPD than OT. The test dose in different series varies

from one to 100 TU. Both 5 and 10 TU are

referred to as intermediate strength. In

addi-tion, patch tests, tuberculin jelly, and puncture

tests (Heaf, Tine) are also in use. There is disagreement as to what constitutes a positive reaction. Five millimeters induration is a

fre-quently mentioned figure, but 6, 8, and 10 mm

have also been used. In 1963, the Committee on Diagnostic Skin Testing of the American

Thoracic suggested arbitrarily

choos-ing a dividing point of 8 to 10 mm. The

prob-lem is compounded by the fact that measure-ment of the indurated area is, itself, inexact

and subject to observer error. Loudon and

Lawson19 and more recently Kieinman2o have

demonstrated significant interpretive bias in the reading of tuberculin tests.

In view of the many variables involved, it

is not surprising that it is difficult to find

re-ports of tuberculin testing after BCG which

correspond exactly to our conditions on dupli-cate exactly our results. In general, our figures for positive reactors are somewhat lower than

most reported studies. This is expected since

our methods have selected those variables

which tend to lessen skin reactivity: use of

Rosenthal vaccine, vaccination in the newborn

period, testing with PPD, and the choice of

5 TU as the critical test and 10 mm induration

as significantly positive.

Testing with 100 TU is far too strong as a

screening procedure; however, it does

demon-strate the persistence of hypersensitivity after

BCC, and it serves to correlate our results with

(4)

EXPERIENCE AND REASON-BRIEFLY RECORDED 627

of PPD, usmg 10 mm and over as positive.

From Figure 3 it may be seen that in a

popula-lion immunized as newborns with Rosenthal strain BCG, by multi-puncture disk, a positive

reaction of 10 mm or more to 5 TU of PPD

after a year of age is highly significant and

very unlikely to be due to the BCG. Thus it is

not only possible to screen these children for

supeninfection, but also their presence should

not interfere with mass tuberculin testing of

children over a year of age or school children.

Tuberculin testing of school beginners on the

Navajo reservation has continued to be both feasible and practical despite over half the children having received BCG.

SUMMARY

Results of tuberculin testing of 250 Navajo

infants and children, vaccinated as newborns with Rosenthal BCG is reported. The incidence of strong reactors to 5 TU of PPD is very low

after one year. It is suggested that tuberculin

testing of BCG-vaccinated children as

screen-ing for tuberculosis, under the conditions

out-lined above, is both feasible and practical. Three cases of pi-imary pulmonary tuberculosis

so discovered are reported.

MARTIN LlFscHrrz, M.D.

Division of Indian Health,

Public Health Service Indiall Hospital

Fort Defiance, Arizona

REFERENCES

1. Robinson, A. : Pulmonary tuberculosis. Pediat. Clin. N. Amer., 4:255, 1957.

2. Finland, NI.: Tuberculosis nuortality and mor-bidity and problems of BCG-vaccination in

the U.S. New EngI. J. Med., 261:699, 1959.

3. Anderson, A. : The case against BCG. Brit.

Med. J., 1:5135, 1959.

4. Taub, J. S., and Haggerty, R. J.: Active

imnlu-nization. New Engi. J. Med., 269:573, 1963.

5. Stein, S. C., and Aronson, J. D. : Pulmonary

tuberculosis among BCG-vaccinated persons.

Amer. Rev. Tuberc., 68:695, 1953.

6. Irvine, K. N. : BCG and Vole vaccination.

Amer. Rev. Tuberc., 74:43, 1956.

7. Snuith, M. : Vaccination against tuberculosis. PEDIATRICS, 24:358, 1959.

8. Rosenthal, S. R., Loewinson, E., Graham, M.,

and Batson, H. C. : BCG-vaccination in

Chi-cago. PEDIATRICS, 28:622, 1961.

9. Indian Health Program: U.S. Public Health

Service. U.S. Department of Health,

Educa-tion and Welfare. Washington, D.C.: U.S.

Government Printing Office, 0-682906, 1963,

p. 25.

10. Eneil, H. : BCG-vaccmation, tuberculin allergy

and tuberculosis in school children. Acta

Paed., 44:1, 1955.

11. Aronson, J. D., Taylor, H., and McGettigen,

M. : Comparisons of some tubercuiins in

BCG-vaccinated and unvaccinated persons.

Amer. Rev. Tuberc., 70:71, 1954.

12. Aronson, J. D., and Taylor, H. C: Trend of

tuberculosis infections among sone Indian

tribes and influence of BCG. Amer. Rev.

Tuberc., 72:35, 1955.

13. Griffiths, M.: Multiple puncture vaccination

in newborns with freeze-dried BCG vaccine.

Brit. Med. J., 2:1116, 1960.

14. Barclay, W. R. : BCC-vaccination. PEDIATRICS,

24:478, 1959.

15. Willis, S., and Vandiviere, M. : Heterogenicity

of BCG. Amer. Rev. Respir. Dis., 84:288,

1961.

16. Lithander, A. : Tuberculin allergy after BCG

in guinea pigs. Acta Path. Microbiol.

Scand. Fasc., 49:165, 1960.

17. Birkhaug, K., Pangborn, M. C., and

Cum-nuerow, E. H. : Studies of purified protein

tuberculin fraction in testing

BCC-vacci-nated subjects. Amer. Rev. Tuberc., 66:335,

1952.

18. Committee on Diagnostic Skin Testing,

Anueri-can Thoracic Society: Tuberculin

skin-test-ing techniques: current status. Amer. Rev.

Respir. Dis., 87:607, 1963.

19. Loudon, R. G., Lawson, R., and Brown, J.: Variation in tuberculin test reading. Amer.

Rev. Respir. Dis., 87:852, 1963.

20. Kieinman, H., Bearman, J. E., Giyer, V. V., and

LaCroix, 0. : A study in variability in

tuber-culin test reading. Amer. Rev. Respir. Dis.,

90:913, 1964.

A Case

Report

of “Cape

Cod”

Rocky

Mountain

Spotted

Fever

with

Multiple

Coagulation

Disturbances

It was not until 1931 that Rumreich et al.1

described Rocky Mountain Spotted Fever in

the eastern United States. Since that time the disease has become well known throughout the eastern half of the country with the exception

of the New England states.2 Since 1938 there

have been 25 reported cases in Massachusetts,5 all of whom contracted the disease in the Cape Cod area. This report will describe a case complicated by thrombocytopenia and

distur-bances of coagulation.

CASE REPORT

A. S. Children’s Hospital Medical Center No.

(5)

4-year-1965;36;624

Pediatrics

Martin Lifschitz

BCG-Vaccinated Children

The Value of the Tuberculin Skin Test as a Screening Test for Tuberculosis among

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(6)

1965;36;624

Pediatrics

Martin Lifschitz

BCG-Vaccinated Children

The Value of the Tuberculin Skin Test as a Screening Test for Tuberculosis among

http://pediatrics.aappublications.org/content/36/4/624

the World Wide Web at:

The online version of this article, along with updated information and services, is located on

American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

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