infection control and hospital epidemiology
june 2007, vol. 28, no. 6
original article
Exposure to Pulmonary Tuberculosis
in a Neonatal Intensive Care Unit: Unique Aspects
of Contact Investigation and Management of Hospitalized Neonates
Joseph Jacob Nania, MD; Jena Skinner, RN; Kathie Wilkerson, RN; Jon V. Warkentin, MD, MPH;
Valerie Thayer, RN; Melanie Swift, MD; William Schaffner, MD; Thomas R. Talbot, MD, MPH
objective. We describe the investigation of a tuberculosis (TB) exposure in which a neonatal intensive care unit (NICU) respiratory
therapist was the index patient, as well as the rationale by which exposed infants were managed and possible explanations for the lack of
transmission to these patients.
design.
setting.
Description of an exposure investigation.
Academic, level IV NICU of a tertiary care children’s hospital.
participants. Contacts of a respiratory therapist with pulmonary TB disease, including household members, healthcare coworkers,
and infant patients.
results. In addition to 5 household contacts, 248 healthcare coworkers and 180 infant patients were identified as possibly exposed
during the 24 days that the index patient worked between December 3, 2004, and January 30, 2005. Tuberculin skin tests (TSTs) were
performed for 233 of the 235 contacts with the greatest degree of exposure (household and coworker contacts) who had a previously
documented negative TST result or whose TST status was unknown prior to the investigation. No cases of latent tuberculosis infection or
TB disease were identified. Because of characteristics of the index case, the exposure duration and setting, the infants’ small lung volumes,
and lack of evidence of transmission to higher-risk contacts, infants were not clinically evaluated or empirically treated for TB disease.
Surveillance for subsequent illness was carried out by primary healthcare providers and parents. No TB disease or unexplained illness in
these infants was reported in the 20 months following the exposure.
conclusion. After limited hospital exposure to a healthcare worker with pulmonary TB disease who is not highly contagious, neonates
can be safely managed without specific evaluation for TB disease or empirical treatment.
Infect Control Hosp Epidemiol 2007; 28:661-665
Although the incidence of tuberculosis (TB) disease in the
United States is at a historical nadir,1 the goal of disease
elimination makes the control of TB disease an issue of continued importance. Nosocomial TB exposures result not only
from infected patients, but also from infected healthcare
workers (HCWs), who account for 3.1% of the reported TB
disease cases in the United States.1 Active TB disease in an
HCW in a neonatal intensive care unit (NICU) can lead to
relatively low-level exposure for a large number of patients
who are at high risk of developing severe disease, should TB
infection occur. We describe a recent case involving a NICU
HCW with TB disease and the management of that individual’s contacts.
methods
Exposure Investigation
On January 25, 2005, a 49-year-old respiratory therapist who
worked exclusively in the NICU was evaluated for a cough
of 2-3 weeks duration. He reported recent flulike symptoms,
but denied fever, night sweats, and chills. He had no exposure
to known or suspected cases of TB disease. His last tuberculin
skin test (TST) for annual employment screening, performed
in November 2003, was nonreactive.
A chest radiograph revealed a 1.2-cm nodule in the left
mid-lung field and an irregular right apical opacity with adjacent pleural thickening (Figure 1). No cavitary lesions were
From the Division of Pediatric Infectious Diseases and Department of Pediatrics (J.J.N.), the Department of Medicine (M.S., W.S., T.R.T.), and the
Department of Preventive Medicine (W.S., T.R.T.), Vanderbilt University School of Medicine, the Department of Infection Control and Prevention (J.S.,
K.W.) and the Occupational Health Clinic (V.T., M.S.), Vanderbilt University Medical Center, and the Tennessee Department of Health (J.V.W.), Nashville,
Tennessee.
Received June 19, 2006; accepted October 4, 2006; electronically published April 20, 2007.
䉷 2007 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2007/2806-0004$15.00. DOI: 10.1086/517975
662
infection control and hospital epidemiology
june 2007, vol. 28, no. 6
exchanges per hour. With the exception of a few negativepressure isolation rooms, all rooms have neutral pressure relationships with the surrounding areas. Any patient who was
in the second NICU on a day that the index patient provided
services in the same room was considered exposed.
Stratification of Exposures
figure 1. Index patient’s chest radiograph from the day of presentation, January 25, 2005. Note the infiltrate in the apex of the
right lung and small nodule in the left mid-lung field.
noted on this radiograph or by subsequent computed tomography. A TST was performed on February 1, and the
HCW was placed on leave from work. At 72 hours, an induration 20 mm had developed at his TST site. Three sputum
specimens were smear-negative for acid-fast bacilli. Staining
of bronchoalveolar lavage fluid specimens, obtained the following week, was negative for acid-fast bacilli. The HCW was
empirically treated with isoniazid, rifampin, pyrazinamide,
and ethambutol. On February 22, cultures of 2 of 3 sputum
samples and cultures of the bronchoalveolar lavage fluid specimen first grew acid-fast bacilli, which were identified as Mycobacterium tuberculosis complex strains by polymerase chain
reaction on February 24. The isolates were susceptible to all
antimicrobials tested. As the period of communicability may
precede symptoms of TB disease,1 we estimated the onset of
contagiousness as December 3, one month prior to symptom
onset.
The index patient had 5 household contacts (all older than
13 years of age) who lived in the same dwelling during the
infectious period and who were evaluated by the local health
department. Work schedules for the index patient from December 3 through February 1 were cross-referenced with those
of other HCWs to determine possible exposure. Working in
the NICU on the same day as the index patient was deemed
an exposure.
Computerized billing data that the index patient was required to generate for his services were used to determine
patient exposure. In the main NICU, patient rooms are single
occupancy, with 10%-20% air recirculation and 6.7 air exchanges per hour. A second NICU has 2 open ward–style
rooms with approximately 5 beds per room. These rooms
have 10%-20% air recirculation and approximately 10 air
A “concentric-circles” approach was used to classify the risk
of transmission of M. tuberculosis to contacts of the index
case.2 Briefly, this approach places those at highest risk of
contracting TB disease in the center circle of contacts. Those
with the next lowest risk are placed in a circle surrounding
the first, and so on, until a target-like diagram is constructed
with the index case in the center (Figure 2). Placement of
individuals in the concentric circle schema is based on several
variables known to affect transmission of TB disease, including the duration and setting of exposure (specifically, volume
and ventilatory exchanges of airspace) and individual contact
characteristics. Evaluation of contacts begins with the center
circle and proceeds outward, stopping where the rate of TST
positivity falls to the expected baseline rate (eg, the baseline
positive TST rate for HCWs in the institution).
The 5 household contacts were at highest risk and placed
in the central circle because of their prolonged exposure to
the index patient in their home and automobiles, which are
relatively confined and poorly ventilated airspaces. The next
circle contained those assigned an intermediate risk and included all exposed HCWs because of their frequent, but
briefer, exposures in the well-ventilated hospital. The outermost circle contained those at lowest risk, the infant patients. The families of exposed patients were also placed in
this same circle; however, family members were often not
present during the brief exposures to the index case. Additionally, some patients were endotracheally intubated and
only breathing air filtered by a ventilator circuit (Airlife Nonconductive Respiratory Therapy Filter [Cardinal Health],
which has a bacterial filtration efficiency of 99.98%) during
encounters. Also noteworthy in predicting risk to the patients
was the very small respiratory minute volume (ie, volume of
air breathed per minute, or “minute ventilation”) of a neonate, which predicts a much lower likelihood of inhaling TB
droplet nuclei, compared with an adult.
TSTs were administered to all available HCWs except those
with a previously documented positive result. A list of patient
contacts was compiled, which included the names and addresses of their parents and their primary care providers.
When it was determined that early evidence of transmission
to higher-risk contacts was lacking, we recommended no TB
disease evaluation or empirical drug therapy for lower-risk
contacts. If TST conversions or TB disease linked to the
exposure had been found subsequently, the need for evaluating and treating lower risk contacts would have been
reconsidered.
management of a nicu tuberculosis exposure
663
figure 2. Risk stratification of individuals exposed to the index patient with tuberculosis (TB) disease, represented with concentric
circles. The factors used for placement in the schema are detailed in the boxes on the right. Outcomes listed in each circle are the proportion
of individuals with positive tuberculin skin test (TST) results out of the total number tested.
results
The Index Patient
The index patient worked a total of 24 days during the estimated period of infectiousness. Directly observed therapy
was administered by the local health department. The index
patient returned to work after 3 weeks of therapy with isoniazid, rifampin, ethambutol, and pyrazinamide. No source
for the index case was found after investigating for links to
known TB disease cases in the hospital and in the community.
Household Contacts
No symptoms consistent with TB disease were found in
household contacts. Four were judged to have had more than
96 hours of exposure per week, and 1 had 48 hours of exposure per week. None developed an induration after TSTs
performed on 3 occasions (in February, May, and July 2005).
All remained clinically healthy.
Healthcare Workers
A total of 248 HCWs were exposed. Nurses and nursing
assistants accounted for 131 of these contacts. The others
were physicians (n p 71) and individuals from environmental services (n p 21), respiratory therapy (n p 12), nutrition/
dietary services (n p 5), radiology (n p 4), and clerical staff
(n p 4).
Of these contacts, 18 had documented positive TST results
prior to the exposure, did not have symptoms consistent with
TB disease, and were asked to return to the Occupational
Health Clinic if symptoms developed subsequently. Seven
contacts no longer worked at the hospital and were unavailable for testing by the institution. Five that were located by
the health department had nonreactive TSTs. Two contacts
were not located. The remaining 223 HCWs had TSTs performed for baseline testing and again at 12 weeks or more
after the last exposure. None had a positive TST result (defined as an induration with a diameter of 5 mm or greater).
No cases of TB disease were identified in HCWs.
Patients
A total of 180 patients were investigated as contacts of the
index case. The services performed by the index patient included maintaining respiratory apparatus or pulse oximeters,
obtaining blood gas analysis specimens, chest physiotherapy,
and administration of inhaled therapy.
Twenty-two exposed patients were hospitalized at the beginning of the investigation, and 12 had died. Their families
were informed of the exposure directly by a neonatologist.
None of these patients were judged to have clinical illness,
chest radiograph findings, or autopsy findings consistent with
TB disease. For patients who had been discharged from the
hospital (n p 146), their primary care provider was notified
by both telephone and mail. After primary care providers
were notified, each family was notified similarly. In all, 144
(80%) of the 180 families were contacted in person or by
telephone. Addresses were available for all patients who were
not currently hospitalized. Seven (4.8%) of 146 letters sent
were returned as undeliverable. Because of the index case’s
sputum smear status, chest radiograph findings, and his fam-
664
infection control and hospital epidemiology
june 2007, vol. 28, no. 6
ily members’ negative TST results, no evaluation for TB disease was recommended for the patients. Primary care providers and families were asked to report subsequent illnesses
that raised concerns about TB disease to the institution. The
notification of primary care providers and families was well
received. Both groups expressed gratitude for the caution and
transparency with which the investigation was conducted.
When final evaluations found no transmission of M. tuberculosis to higher risk contacts, the patients’ families and
primary care providers were informed by mail and reminded
to report illnesses suspected of being TB disease. Twelve
(7.1%) of 168 follow-up letters sent to families were returned
as undeliverable. Only 4 (2.2%) of 180 families could not be
reached at least once. No associated cases of TB disease, latent
TB infection, or unexplained illness in contacts were reported
in the subsequent 20 months.
discussion
The results of this investigation are consistent with other
reports which have shown that transmission of M. tuberculosis
to hospitalized neonates was not identified3-6 or was rare7-9
after exposure to an adult with pulmonary TB disease. The
likely reason for the rarity of transmission to neonates exposed in the hospital is not known, but presumably it is
multifactorial. Characteristics of the index case and the environment in which exposure occurs are clearly important.
Cavitary disease and smear-positive sputum are 2 characteristics proven to increase M. tuberculosis transmission.1,10-14
However, other reports of nursery exposures noted that the
index patients possessed one3,6-8 or both4,5,9 of these factors
without frequent transmission to neonate patients. Moreover,
our index patient lacked both factors. The hospital setting
affords active ventilation, larger air volumes, and often only
brief duration of exposure to a HCW with undiagnosed TB
disease. All of these factors have been shown to predict lower
transmission risk,12,15,16 and Centers for Disease Control and
Prevention guidelines advocate using such factors to prioritize
contacts for clinical evaluation.1,14
Infants clearly have a higher risk of developing TB disease,
including disseminated disease, once infected.17-20 Presumably, the higher risk of developing TB disease should decrease
the threshold for initiating evaluation.1,14 It has been suggested
that infants are more likely than older persons to become
infected after exposure to M. tuberculosis, but this hypothesis
appears to be based on the putative role of immature alveolar
macrophage defenses, rather than clinical data.9
A biologically plausible counterargument can be made that
infants are less likely to be infected than older people. The
risk of inhaling an infectious dose of M. tuberculosis is related
not only to the air density of droplet nuclei, but also to the
alveolar respiratory minute volume of the patient. The estimated respiratory minute volume of our patients (most of
whom weighed less than 2 kg) was 250-500 mL, compared
to 6,000 mL in an average adult.21 Available clinical data come
from studies of household exposures to TB disease in which
rates of infection in infants and young children have been
shown to be similar19,22 or significantly lower,11,23 compared
with older children and adults after exposure to M. tuberculosis. This might be due to a lower sensitivity of TSTs in
infants and higher rates of exposure to TB disease outside
the home for older contacts; however, these data do not support the notion that exposed infants are more likely to be
infected than adults.
If neonates are not more (and are conceivably less) likely
than adults to become infected with M. tuberculosis given a
similar exposure, the crucial issue is determining what constitutes an exposure sufficient to warrant specific diagnostic
evaluation. A lower risk of contagiousness in our index patient was predicted by negative sputum smear results and the
lack of cavitary disease. In addition, after using a “concentriccircles” approach to stratify risk to contacts, we were most
reassured by the lack of transmission to persons with a greater
degree of exposure and larger respiratory minute volume.
Because TST results cannot reliably be used to rule out TB
infection in neonates (especially premature infants, for whom
there are no data on TST validity), empirical treatment with
isoniazid is recommended for infants with an M. tuberculosis
exposure.1 Although isoniazid is generally well tolerated by
infants,3,4,17 we opted against taking the risk of treating 168
neonates, most of whom were premature and had multiple
medical problems. This decision was based on the successful
experience of others who did not treat in similar situations5-7 (and personal communication, Jeffrey R. Starke, MD,
February 2005) and our estimation that our patients were at
exceedingly low risk of acquiring TB disease or infection from
their exposure.
Recently published Centers for Disease Control and Prevention documents provide a thorough overview of TB disease control and contact investigation in both community
and healthcare settings.1,14,24 However, the guidelines do not
take into account the nuances of exposure in specialized settings, such as a NICU. Given the vulnerability of this patient
population to developing TB disease, the potential for more
than 1,000 infants to be affected by a single case,7,8 and the
generally low level of exposure that occurs in a NICU, specialized guidelines to standardize management of infants exposed to M. tuberculosis in the healthcare setting may be
warranted.
acknowledgments
Potential conflicts of interest. All authors report no conflicts of interest relevant to this article.
Address reprint requests to Joseph Jacob Nania, MD, 1161 21st Avenue
South, D-7235 Medical Center North, Nashville, Tennessee 37232 (jake
.nania@vanderbilt.edu).
management of a nicu tuberculosis exposure
Presented in part: 16th Annual Scientific Meeting of the Society for Healthcare Epidemiology of America (SHEA); Chicago, Illinois; March 19, 2006
(Abstract 115).
12.
references
13.
1. Taylor Z, Nolan CM, Blumberg HM. Controlling tuberculosis in the
United States. Recommendations from the American Thoracic Society,
CDC, and the Infectious Diseases Society of America. MMWR Recomm
Rep 2005; 54(RR-12):1-81.
2. Etkind S, Veen J. Contact follow-up in high- and low-prevalence countries. In: Reichman LB, ed. Tuberculosis: A Comprehensive International
Approach. 2nd ed. New York: Marcel Dekker Inc., 2000:377-399.
3. Sen M, Gregson D, Lewis J. Neonatal exposure to active pulmonary
tuberculosis in a health care professional. CMAJ 2005; 172:1453-1456.
4. Light IJ, Saidleman M, Sutherland JM. Management of newborns after
nursery exposure to tuberculosis. Am Rev Respir Dis 1974; 109:415-419.
5. Burk JR, Bahar D, Wolf FS, Greene J, Bailey WC. Nursery exposure of
528 newborns to a nurse with pulmonary tuberculosis. South Med J
1978; 71:7-10.
6. Keim LW. Letter: Management of newborns after nursery exposure to
tuberculosis. Am Rev Respir Dis 1974; 110:522-523.
7. Steiner P, Rao M, Victoria MS, Rudolph N, Buynoski G. Miliary tuberculosis in two infants after nursery exposure: epidemiologic, clinical, and
laboratory findings. Am Rev Respir Dis 1976; 113:267-271.
8. Mycobacterium tuberculosis transmission in a newborn nursery and maternity ward—New York City, 2003. MMWR Morb Mortal Wkly Rep
2005; 54:1280-1283.
9. Nivin B, Nicholas P, Gayer M, Frieden TR, Fujiwara PI. A continuing
outbreak of multidrug-resistant tuberculosis, with transmission in a hospital nursery. Clin Infect Dis 1998; 26:303-307.
10. Reichler MR, Reves R, Bur S, et al. Evaluation of investigations conducted to detect and prevent transmission of tuberculosis. JAMA 2002;
287:991-995.
11. Marks SM, Taylor Z, Qualls NL, Shrestha-Kuwahara RJ, Wilce MA,
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
665
Nguyen CH. Outcomes of contact investigations of infectious tuberculosis patients. Am J Respir Crit Care Med 2000; 162:2033-2038.
Bailey WC, Gerald LB, Kimerling ME, et al. Predictive model to identify
positive tuberculosis skin test results during contact investigations. JAMA
2002; 287:996-1002.
Liippo KK, Kulmala K, Tala EO. Focusing tuberculosis contact tracing
by smear grading of index cases. Am Rev Respir Dis 1993; 148:235-236.
Guidelines for the investigation of contacts of persons with infectious tuberculosis. Recommendations from the National Tuberculosis Controllers
Association and CDC. MMWR Recomm Rep 2005; 54(RR-15):1-47.
Gerald LB, Tang S, Bruce F, et al. A decision tree for tuberculosis contact
investigation. Am J Respir Crit Care Med 2002; 166:1122-1127.
Catanzaro A. Nosocomial tuberculosis. Am Rev Respir Dis 1982; 125:
559-562.
Vallejo JG, Ong LT, Starke JR. Clinical features, diagnosis, and treatment
of tuberculosis in infants. Pediatrics 1994; 94:1-7.
Hussey G, Chisholm T, Kibel M. Miliary tuberculosis in children: a review
of 94 cases. Pediatr Infect Dis J 1991; 10:832-836.
Gessner BD, Weiss NS, Nolan CM. Risk factors for pediatric tuberculosis
infection and disease after household exposure to adult index cases in
Alaska. J Pediatr 1998; 132:509-513.
Marais BJ, Gie RP, Schaaf HS, Beyers N, Donald PR, Starke JR. Childhood
pulmonary tuberculosis: old wisdom and new challenges. Am J Respir
Crit Care Med 2006; 173:1078-1090.
Luce JM. Respiratory monitoring in critical care. In: Cecil RL, Goldman
L, Bennett JC, eds. Cecil Textbook of Medicine. 22nd ed. Philadelphia:
W.B. Saunders, 2004:598-602.
Madhi F, Fuhrman C, Monnet I, et al. Transmission of tuberculosis from
adults to children in a Paris suburb. Pediatr Pulmonol 2002; 34:159-63.
Soysal A, Millington KA, Bakir M, et al. Effect of BCG vaccination on
risk of Mycobacterium tuberculosis infection in children with household
tuberculosis contact: a prospective community-based study. Lancet 2005;
366:1443-1451.
Jensen PA, Lambert LA, Iademarco MF, Ridzon R. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care
settings, 2005. MMWR Recomm Rep 2005; 54:1-141.