Childhood Tuberculosis in North Caroiina: A Study of the Opportunities
for intervention in the Transmission of Tubercuiosis to Children
ROBERT J. NOLAN, JR., MD
Abstract: New cases ol ttiberculosis in children continue to
appear. A retrospective review of the medical records of a repre-
sentative satuple of such cases occurring from 1977 through 1981 was
conducted to gain an understan.ling of why this preventable disease
continues to occur in North Carolina children. Three per cent of
cases were detected by routine screening; 17 percent were diagnosed
after the child's symptomatic presentation; and 80 per cent after
contact screening. However, 14 per cent of cases detected by contact
Introduction
Despite nearly a century of public health intervention
and the availability of specific chemotherapy for more than 30
years, tuberculosis remains a relatively unusual but impor-
tant cause of morbidity in children.'-^, New cases of tuber-
culosis in children continue to appear in North Caroiira, In
recent years, an average of 47 such cases per year were
reported. In an attempt to identify the variables associated
with tuberculous disease in children, this study examtned the
demographic characteristics of reported childhofju cases in
North Carolina and the circumstances of deteilion. diagno-
sis, and management. Certain clinical and epidemiologic
features of childhood tuberculosis in North Carolina are
described.
Methods
Data were obtained in two phases: I) data on cases
statewide were obtained from the North Carolina Tubercu-
losis Control Division (NCTCD); 2) additional data were then
gathered on cases in selected counties.
A tuberculosis case is defined as any child in whom the
presence of Mycobacterium ttiberculosis has been confirmed
by bacteriologic studies, or. in the absence of bacteriologic
confirmation, any child who meets all of the following
criteria: 1) a significant tuberculin skin test reaction; 2)
appropriately abnormal utistable chest x-rays or clinical or
pathologic evidence of disease or both; 3) receiving a course
of chemotherapy with two or more antituberculous medica-
tions. These are the standard Centers for Disease Control
(CDC) criteria for the case definition of tuberculous disease.
The reporting criteria specifically exclude individuals who
are recent skin test converters without evidence of active
disease and individuals for whom the attending physician
believes single drug therapy for active disease is sufficient.
The NCTCD requires the following data to be reported
to it for each case; name, age, sex, race (White, Black,
Address reprint requests to Robert J. Nolan, Jr., MD. Department of
Pediatrics, University of Texas Health Science Center at San Antonio, 7703
Floyd Curl Drive, San Antonio, TX 78284. At the time this study was
conducted. Dr. Nolan was a Robert Wood Johnson Foundation Fellow in
Genera] Academic Pediatrics at Duke University Medical Center. This paper,
submitted to the Journal March 5, 1985, was revised and accepted for
publication August 22, 198.5.
Editor's Note: See also related editorial p 12 this issue.
© 1985 American Journal of I^jblic Health OO9O-OO36/85$1.5O
26
screening developed disease while receiving isoniazid prophylaxis
for a positive tuberculin test; and 19 per cent of cases detected by
contact screening developed disease while under surveillance, but
not receiving i.soniazid prophylaxis, as tuberculin negative contacts
of known infectious cases. Adherence to accepted recommendations
for prophylaxis should reduce the childhood tuberculosis case rate.
(Am J Publi'* Health 1986; 76:26-30.)
American Indian, or Asian origin), county of residence, site
of disease, culture status (positive, negative, or not done),
and report.ng agency (private physician, county health de-
partment, state hospital, private hospital, etc.). These data
(hereafter referred u^ as the NCTCD data variables) were
made available tc the author on all 235 cases 0 through 14
years of age f-epor ed in North Carolina from January 1, 1977
through Decembor 31. 1981. They were used to create an
incidence map of disease (Figure 1).
To select a sample of counties for further data collection,
counties were divided into three groups: counties with no
cases; low incidence counties, with an average yearly inci-
dence below the statewide mean of six cases per 100.000: and
high incidence counties with an average yearly incidence
greater than the statewide mean. A pilot study was conducted
in two high incidence and one low incidence counties. From
their respective high and low incidence county groups in the
eastern two-thirds of North Carolina (counties within a
150-mile radius of Durham County), five additional high
incidence counties and six additional low incidence counties
were randomly selected, creating a total sample of 14 coun-
ties evenly divided between high and low incidence counties
(Figure I).
Since state policy provides for free diagnostic services
and anti-tuberculous medications for suspect cases and their
contacts, county health departments (CHD) maintain exten-
sive records on reported cases. Additional patient data on
reported cases (history of presentation, family history,
symptomatology, chest x-ray status, bacteriologic status,
hospitalization history, etc.) were obtained at their local
county health departments by an on-site. retrospective,
medical record review. Specific data regarding compliance
with medication regimens were unavailable. The medical
records of all 118 reported cases in the 14 selected counties,
representing 50.2 per cent of all cases reported statewide
during the survey period, were examined.
Rates of change in the incidence of disease during the
survey period were determined from the linear regression of
the logarithms of the annual incidence rates to ensure
comparability with recent CDC analyses of national data.
Results
Statewide Data
There were 235 children 0 through 14 years of age
reported as cases from 1977 through 1981; 179 of the children
(76.2 per cent) were Black, 48 (20,4 per cent) were White, 6
AJPH January 1986, Vol. 76, No. 1
 CHILDHOOD TUBERCULOSIS IN NORTH CAROLINA

Do
L J 0.1-6 Average annual incidence rate * Durham County
^ 6.1+ (cases per 100,000) in children
• Survey County
0-14 years of age, 1977-1981
FIGURE I—Average Annual Incidence of Tuberculosis \n Children 0 through 14 Years of Age, North Carolina, 1977-81

(2.5 per cent) were of Asian origin, and 2 (0.9 per cent) were
American Indians. No Hispanic surnamed children
werereported. Female cases outnumbered male cases slightly
(125/235. 53 per cent v 110/235, 47 per cent).
The incidence of tuberculosis changed by an average of
-1.9 per cent per year from 1977 to 1981 (Table 1). The
change in incidence averaged +0.02 per cent per year in the
White population and - 1.9 per cent per year in the non-White
population. When cases of Asian origin were excluded from
the data analysis, the rate of change in the total disease
incidence increased to -3.6 per cent per year and in the
non-While population to -2.5 per cent per year.
Nonpulmonary cases represented 20 per cent (47/235) of
the total. White children were more likely to have
nonpulmonary disease than non-White children (15/48, 31 per
cent V 32/187, 17 per cent), a difference due to the greater
frequency of lymphatic nonpulmonary disease in White
children than in non-White children, (12/48, 25 per cent v
15/187, 8 per cent: difference = 17 per cent, 95 per cent
confidence intervals 4 per cent. 30 per cent).
The proportion of cases who underwent bacteriologic
studies and the rate of positive cultures among those studied
declined from 1977 to 1981 (Figure 2). This decline was
unrelated to race, age, or sex. Bacteriologic studies were
obtained with similar frequency in nonpulmonary and pul-
monary cases (34/47, 72 per cent v 141/188, 75 per cent); but
when bacteriologic studies were obtained, positive results
were more common in nonpulmonary cases than pulmonary
cases (27/34, 79 per cent v 45/141, 32 per cent; difference -
TABLE 1—Tuberculosis Incidence Rates' for Children In North Carolina, 1977-S1
47 per cent, 95 per cent confidence intervals 31 per cent, 63
per cent).
County Survey Patient Data
The 118 cases whose medical records were reviewed did
not differ from the entire population of cases in the eastern
two-thirds of North Carolina with respect to the NCTCD data
variables. None of the sample cases were children of migrant
farm workers. Medical records were available for all 118
cases and were complete in 109 cases. The nine cases for
whom only partial records were available did not differ from
the remaining sample cases with respect to any NCTCD data
variable. Ten cases (9 per cent of those with complete charts)
were either misreported to the NCTCD or did not meet the
CDC case definition (three adult cases were reported as
children; two cases were double reported by different agen-
cies; two lymphatic cases had culture isolates identified as
Mycohacterium avium-intracellulare; and three were culture
negative children with insufficient clinical, roentgenologic, or
tuberculin test evidence of disease). The ten noncases,
excluding the misreported adults, did not differ from the
cases with respect to any NCTCD data variable except that
they were more likely to be residents of low incidence
counties than were the cases (6/7, 86 per cent v 37/99, 37 per
cent; difference = 49 per cent, 95 per cent confidence
intervals 22 per cent, 76 per cent). Noncases and cases with
only partial records were excluded from further analysis
leaving a sample of 99 valid cases.
All cases had tuberculin skin test reactions (PPD, 5TU
by the Mantoux method) greater than 10 mm induration with

Year Total Rate White Rate Black Rate American Indian Rate Asian Rate Total Non-White Rate

1977 4.0 1.1 11.5 4.9 9.0 11.4

1978 3.1 1.1 9.2 0.0 0.0 8.7
1979 2,5 0.6 7.5 0.0 9.0 7.4
1980 4.0 1.4 10.2 4.9 26.9 10.7
1981 3.2 0.8 9.6 0.0 9.0 9.3
Average Annual 1977-81 3.3 1.0 9.6 1.9 10.8 9.5
Total Cases () (235) (48) (179) (2) (6) (187)

'Cases per 100.000 children age 0 througfi 14 years.

AJPH January 1986, Vol. 76, No. 1 27


FIGURK 2—PercenUge or Cases 0 throuRh 14 Years of Ane wilh Bacleriologic
Studies Obtained • • ; Percentage ot Positive Studies amoni; those (:a.se<i
Studied A A; and Percentage of Cases with Positive Bacteriologic Studies
an increase of at least 6 mm over any previous reaction. For
those cases in which exact measurements were noted (n =
78). the mean cutaneous induration was 18.5 mm, (range
10-70 mm); 81 per cent (63/78) of the reactions were 15 mm
or greater.
Three cases (3 per cent) were detected and diagnosed
after routine screening (RS); 17 cases (17 per cent) were
diagnosed after the child's symptomatic presentation to a
physician (SPP) with clinical signs referrable to tuberculosis,
and 79 cases (80 per cent) were detected after contact
screening (CS) of the child by CHD personnel in response to
a reported case of disease. All cases detected by routine
screening and 77 per cent (61/79) of cases detected by contact
screening were asymptomatic.
Medical history disclosed the identity of the source case
in 10 of the children diagnosed after symptomatic presenta-
tion to a physician. Medical history failed to reveal the source
of disease in seven cases detected by SPP and all three cases
detected by RS. In four instances in which there was no
source revealed by history, the diseased child (one detected
by RS and three detected by SPP) served as an index case
leading to the detection of diseased adults. Nearly all (98 per
cent. 58/59) of the index cases leading to the CS detection of
children and the historically revealed source cases were
adults; 88 per cent (51/58) of these adults were household
contacts.
Sixty-seven per cent of the CS-detected cases (53/79) had
positive tuberculin tests and clinical or chest x-ray evidence
of disease at their initial encounter for contact screening. An
additional 14 per cent (11/79) had positive tuberculin tests at
their initial encounter without clinical or chest x-ray signs of
disease. These II children were placed on secondary
isoniazid prophylaxis but developed signs of disease later
(mean - 97 days, range 22-191 days).
Nineteen per cent of the CS-detected cases (15/79) had
a negative tuberculin test at their initial encounter. These
children were followed with skin tests at three-month inter-
vals, or when clinically indicated, without receiving primary
isoniazid prophylaxis while remaining in close contact with
(he diseased individual who had prompted the contact screen-
ing. All were subsequently discovered to have positive skin
tests and evidence of disease (mean = 113 days, range:
37-154 days) after initial contact screening. Thus 33 per cent
(26/79) of the cases detected by contact screening (26 per cent
[26/99] of all cases) developed disease while on secondary
prophylaxis, or after failure to receive primary prophylaxis.
28
These cases, in which disease developed while the child was
under surveillance, did not differ from other cases in the
NCTCD data variables examined, or in ultimate severity of
chest x-ray or clinical involvement. They were uniformly
distributed over the period of the survey.
The circumstance of detection (CS v SPP v RS) was
unrelated to race, age, sex, or county of residence. Cases
with nonpulmonary involvement were more likely to have
been detected after SPP than CS (6/17, 35 per cent v 5/79, 6
per cent; difference ^ 29 per cent, 95 per cent confidence
intervals 6 per cent, 52 per cent).
Chest x-ray involvement at diagnosis was more often
mild or moderate than severe. Mild chest x-ray involvement
(significant unilateral or bilateral hilar or paratracheal
adenopathy) was present in 42 (42 per cent); moderate
involvement (hilar or paratracheal adenopathy with segmen-
tal infiltrates or collapse) in 37 (37 per cent), and severe
involvement (miliary or cavitary disease or moderate in-
volvement with recurrent pleural effusions) in 8 (8 per cent).
Seven chest x-rays (7 per cent) were read as "positive" or
"consistent with the clinical diagnosis" without further
elaboration; 5 (5 per cent) were read as negative (all lym-
phatic nonpulmonary cases). Severity of chest x-ray involve-
ment was unrelated to circumstance of diagnosis, race, age,
or sex.
Specimens were obtained for culture with similar fre-
quency in cases with mild chest x-ray involvement as
opposed to moderate or severe involvement (26/42. 62 per
cent V 35/45, 78 per cent). Cultures were positive with similar
frequency in the two groups (8/26, 31 per cent v 13/35, 37 per
cent). Cases under 5 years of age were as likely to have
cultures obtained as those over 5 years (34/51. 67 per cent v
35/48, 73 per cent) and those cultures were as likely to be
positive in the younger age group as in the older (11/34, 32 per
cent V 14/35, 40 per cent).
Culture rate and results were unrelated to race, sex, or
county of residence. Cases detected by SPP were more likely
to have had bacteriologic cultures obtained than cases
detected by CS (16/17. 94 per cent v 51/79, 65 per cent;
difference - 29 per cent, 95 per cent confidence intervals 14
per cent, 44 per cent) and those cultures were more likely to
have been positive (10/16, 63 per cent v 15/51, 29 per cent;
difference = 34 per cent, 95 per cent confidence intervals 7
per cent, 61 per cent). No culture isolate demonstrated
primary drug resistance to isoniazid, rifampin. or para-
aminosalicylic acid.
Most cases (51 per cent, 51/99) were hospitalized at or
shortly after the time of diagnosis. Seventy-five per cent of
these (38/51) were hospitalized at the North Carolina State
Sanitorium and the remainder at community or at teaching
hospitals. Although the two hospitalized groups did not differ
with respect to demographic characteristics, circumstances
of detection, presence of symptoms, chest x-ray or culture
status, the mean length of hospitalization was substantially
longer at the State Sanitorium than at other hospitals; 46 days
V 9 days, difference = 37 days, 95 per cent confidence
intervals 15 days, 59 days. In no case was disease the result
of reactivation, and there was no mortality.
Discussion
In the 15 years prior to 1977,'-the national tuberculosis
case rate for children 0 through 14 years of age declined
relatively more rapidly (8.8 per cent per year) than the total
case rate (4.4 percent per year). However, from 1977 through
1981, the lastfiveyears for which complete data are available.
AJPH January 1986. Vol, 76. No, 1

national childhood case rates increased 0.2 per cent p y
while the total case rates continued to decline nearly 3.5 per
cent per year. The stability of childhood case rates has been
attributed to an increased incidence of disease in Hispanic
children and the influx of Indochinese refugees in the late
1970s.'
Childhood tuberculosis case rates in North Carolina
declined an average of 1.9 per cent per year from 1977
through 1981. Although subtracting the Hispanic cases from
the national White case rates and the Indochinese refugee
cases from the national non-White case rates for the period
1977-81 returned the average annual rate of decline to the
pre-1977 average of 8.8 per cent per year, an eflFect of similar
magnitude was not evident in North Carolina. The indigenous
childhood population of North Carolina experienced a slower
decline in the case rate than the indigenous national popu-
lation.
This slower rate of decline is unlikely to have been due
to an increase in overdiagnosis. Noncases among the children
reported were uniformly distributed during the study period.
Although the proportion of cases with bacteriologic confir-
mation declined during the study period partially as a result
of a decrease in the procurement of cultures, it averaged 31
per cent, which is comparable to the 20 per cent-30 per cent
range found nationally during the same period.^ Diagnostic
confusion with disease caused by atypical Mycobacteria (to
which skin test sensitivity is common in eastern North
Carolina),^ was probably minimal in view of the clinical
characteristics of the cases reported. Moreover, the mean
skin test induration was 18.5 mm, similar to the mean
indurations of 16 to 17 mm reported for series of
Mycobacterium tuberculosis culture positive patients.''
Routine screening was only of minor importance in the
detection of cases (3 per cent, or about 0.9 cases per 1,000,000
children per year). These data do not address the continuing
controversy as to the efficiency and effectiveness of routine
screening with regard to converter detection and prevention
of disease.'' It is interesting to speculate, however, since
childhood converters and childhood cases probably acquire
their infection from the same group of diseased adults, that
routine screening may also be less important than contact
screening in (he detection of converters.
The vast majority of cases, 97 per cent, were detected by
means other than routine screening. Contact screening was
responsible for the detection of 80 per cent of cases. Through
contact screening, most cases were detected prior to the
onset of symptoms. Thus prompt reporting of diseased adults
to public health authorities was the single most important
factor in the early detection of childhood cases. Although
only 17 per cent of cases were diagnosed after the child's
symptomatic presentation to a physician, many of these cases
were nonpulmonary and required familiarity with the multi-
ple presentations of tuberculosis.
A small group of children, 14 per cent of those cases
detected by contact screening, developed disease while on
secondary isoniazid prophylaxis for a positive tuberculin
test. Since the total number of tuberculin positive children
detected by contact screening and placed on prophylaxis is
unknown, it is possible that the cases that failed prophylaxis
represent the biological failure rate of isoniazid prophylaxis,
which has been estimated by Hsu as no greater than 0.3 per
cent.^ A more likely explanation, however, is lack of com-
pliance with the prescribed prophylaxis.
Of greater concern is the development of disease in
tuberculin negative contacts (19 per cent of all cases detected
AJPH January 1986, Vol. 76, No. 1
CHILDHOOD TUBERCULOSIS IN NORTH CAROLINA
by contact screening) who were followed without primary
isoniazid prophylaxis. The American Academy of Pediatrics
and the American Thoracic Society recommend isoniazid
prophylaxis for three months for tuberculin negative children
remaining in a potentially infectious environment, with fur-
ther skin testing at the end of the three-month period.^** The
recommendations are based upon several facts: contacts can
be infected and be initially tuberculin negative since skin test
sensitivity requires three to eight weeks to develop after
exposure^; children progress from infection to disease with
greater frequency than adults'"; and the severe forms of
disease—meningitis and miliary disease—usually occur with-
in the first several months after the infecting exposure."
Isoniazid prophylaxis prevents progression to disease in
infected tuberculin negative contacts and decreases the
frequency of development of infection and skin test conver-
sion in uninfected tuberculin negative contacts.'''-" Our
data clearly support the use of isoniazid prophylaxis for
tuberculin negative contacts as a possible means of reducing
the childhood case rate. The need for prophylaxis of tuber-
culin negative contacts has been increased by the recent
trend toward greater use of outpatient care for adults with
positive sputum cultures.''*
The results of this study indicate that the decision to
obtain cultures should not be influenced by the severity of
chest x-ray presentation or the age of the case at diagnosis.
Although there were no cases of primary drug resistance
among the survey cases, the importance of vigorous culturing
is emphasized by the national primary drug resistance rate of
14 per cent among children.'''
In summary, childhood tuberculosis case rates in North
Carolina continue to decline slowly. Investigation of contacts
of adult cases is the most important method of childhood case
detection. However, two groups of cases detected by such
investigation developed disease while under surveillance.
Careful monitoring of compliance with isoniazid prophylaxis
and adherence to accepted recommendations for isoniazid
prophylaxis for tuberculin negative contacts should reduce
the childhood tuberculosis case rate.
ACKNOWLEDGMENTS
This work was supported, in part, hy the Robert Wood Johnson Foun-
dation Program for Academic Developmeni in General Pediatrics. The aulhor
(hanks Jim Jones. North Carolina Tuberculosis Control Division, and the
Counly Public Health Nurses wiihoul whose cooperation this study cuiild not
have been done. The author acknowledges Dr. Laura T. Gulman for sugges-
tions, Sandra Funk for knowledgeable statistical consultation, and Dr. TTiomas
E, Frothingham for his suggestions, advice, criticism, and review of the
manuscript. This study was presented in part at the General Pediatrics
Academic Development Program annual meeting sponsored by the Robert
Wood Johnson Foundation, Princeton, NJ, June 7-9, 1984.
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IATPM Announces the Luther L. Terry Preventive Medicine Fellowship

The Association of Teachers of Preventive Medicine has announced a two-year senior level
position for a physician to provide national leadership in the development of preventive medicine in
primary care. The fellowship is sponsored by the Association of Teachers of Preventive Medicine
(ATPM), in cooperation with the Society of Teachers of Family Medicine (STFM) and the Society for
Research and Education in Primary Care Internal Medicine (SREPCIM).
The Fellow will serve as senior technical and policy advisor to the Deputy Assistant Secretary for
Health (Director, Disease Prevention and Health Promotion), US Public Health Service, in matters
relating to prevention priorities and programs in clinical settings. The Fellow will also serve as a
national liaison and counsel for initiatives in preventive medicine in primary care which major national
professional organizations and Ihe Office of Disease Prevention and Health Promotion (ODPHP)
consider most important. In this role, the Fellow will work closely with staff and leadership of the
ATPM, SREPCIM. and the STFM, and other national preventive medicine/primary care organizations.
Qualifications are as follows:
Required: MD degree with Board Certification in primary care and/or preventive medicine
disciplines; current faculty appointment in a health sciences school at associate or full professor level
(clinical or tenure-track) or an equivalent level position in a health organization; superior oral and
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The application deadline is January 15. 1986. Salary is $70,0(K) per annum with ample travel funds.
The fellowship term will be two years and it is understood that the fellow will have assurance from his/
her parent institution that he/she may return to that original (or a comparable) position following the
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application procedures about the Luther L. Terry Fellowship position, please contact:

Dennis J. Barbour, JD, Executive Director

ATPM
1030 15th St., NW, Ste. 1020
Washington, DC 20005
(202) 682-1698

30 AJPH January 1986, Vol. 76. No. 1