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Nosocomial Transmission of Congenital Tuberculosis in a Neonatal Intensive Care Unit

  1. Maryanne Crockett1,
  2. Susan M. King1,
  3. Ian Kitai1,
  4. Frances Jamieson5,
  5. Susan Richardson4,
  6. Patricia Malloy1,
  7. Barbara Yaffe6,
  8. Donna Reynolds5,
  9. Jonathan Hellmann2,
  10. Ernest Cutz3,
  11. Anne Matlow1,4, and
  12. Outbreak Investigation Team
  1. 1Division of Infectious Diseases, Toronto
  2. 2Division of Neonatology, Department of Paediatrics, Toronto
  3. 3Department of Pathology, Toronto
  4. 4Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto
  5. 5Microbiology, Laboratories Branch, Ontario Ministry of Health and Long-Term Care, Toronto
  6. 6Toronto Public Health, Toronto
  7. 7Durham Region Health Department, Whitby, Ontario, Canada
  1. Reprints or correspondence: Dr. Anne Matlow, The Hospital for Sick Children, 555 University Ave., Toronto, ON, Canada M5G 1X8 (anne.matlow{at}sickkids.ca).
 
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Abstract

Congenital tuberculosis is uncommon, and nosocomial transmission from a congenitally infected infant to another infant has not been reported in the English literature. We report an investigation of 2 infants with tuberculosis who were cared for in the same neonatal intensive care unit. Isolates from both infants were genetically indistinguishable. Transmission between the 2 infants was likely due to contaminated respiratory equipment.

Congenital tuberculosis is rare, with ∼340 cases described in the literature [1–20]. We describe the outbreak investigation associated with a case of nosocomial transmission of tuberculosis from a congenitally infected infant to another infant.

Patient 1. Patient 1 was born 15 December 2001 by spontaneous vaginal delivery at 25 weeks' gestation to a healthy 42-year-old woman (gravida 5, para 3, spontaneous abortion) and weighed 800 g. The infant was transferred to the neonatal intensive care unit (ICU) on 19 December amid development of numerous complications and remained until death on 4 February 2002. Histopathologic examination of autopsy tissue specimens revealed disseminated tuberculosis with necrotizing pneumonitis, lymphadenitis, and hepatosplenic abscesses. Tissue specimens tested positive for acid-fast bacilli by Ziehl-Neelson staining. Mycobacterium tuberculosis was detected by nucleic acid amplification assay (Mycobacterium tuberculosis Direct [MTD] Test, Gen-Probe; California), and cultures of tissue specimens grew M. tuberculosis (figure 1).

Figure 1
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Figure 1

Micrograph of a Zeehl-Neelson stain of acid-fast bacilli in a lung specimen obtained at the autopsy of patient 1

Patient 2. Patient 2 was born at 33 weeks' gestation on 19 January 2002 to a 25-year-old (gravida 5, para 0) and weighed 2998 g. The infant was transferred to our neonatal ICU for treatment of respiratory distress syndrome and ventilated for 1 week before transfer back to the community hospital.

The infant was readmitted to the community hospital on 8 April 2002 with a 5-day history of cough and fever. Treatment with ampicillin, cefotaxime, and clarithromycin was initiated. Progressive respiratory distress developed, leading to the infant's transfer to the Hospital for Sick Children on 12 April 2002. A chest radiograph showed miliary disease with a right upper lobe cavitary lesion. Tuberculosis was considered unlikely because no risk factors were identified.

The infant's condition deteriorated on 13 April 2002, and the infant required intubation. Bronchoalveolar lavage (BAL) fluid samples revealed acid-fast bacilli. Anti-tuberculosis therapy was initiated. Specimens of BAL fluid and CSF were found to be positive for M. tuberculosis by nucleic acid amplification assay and culture. The infant was treated with 4 drugs and steroids for tuberculosis meningitis and discharged home on 3 June 2002 to complete 12 months of therapy.

Methods. The diagnosis of tuberculosis for both infants was made within a 24-h period: for patient 1, by final autopsy results that were reported 14 April, and, for patient 2, by results of nucleic acid amplification assay of BAL fluid samples on 13 April. A multidisciplinary outbreak investigation team was urgently assembled to investigate and manage a suspected outbreak and prevent further transmission.

The mother of patient 1 had emigrated from Southeast Asia 20 years earlier, after living in refugee camps for 2 years. Although asymptomatic during her child's hospitalization in the neonatal ICU, the mother developed a cough and sterile pyuria several weeks later. A tuberculin skin test (TST) and chest radiography were performed, and she was referred for further investigation. Three adult siblings of patient 1 were also evaluated by TST, but the father was estranged and not assessed. The parents of patient 2 were asymptomatic for tuberculosis. They were evaluated by TST and chest radiography in April 2002 and again 3 months later.

Health care workers, family members, and visitors of neonatal ICU infants were evaluated as possible sources of transmission and as contacts of the infected neonates. Those who had spent at least 8 cumulative hours in the neonatal ICU during hospitalization of patient 1 were assessed by either the Occupational Health Department of the Hospital for Sick Children or their local public health units [21]. Hospital engineers reviewed the neonatal ICU's ventilation system. Reprocessing procedures for all equipment that was possibly used while caring for the 2 infants were reviewed.

The first priority of this investigation was to identify other potentially infected newborns. Because the 2 patients had been located in different rooms in the ICU, all infants who had been in the neonatal ICU during their hospitalizations required evaluation (n = 132). Ten of these infants were deceased, and these deaths were reviewed. Of the remaining 122 infants, 15 were hospitalized or living in other provinces, and 107 were at home. Special assessment clinics were convened at the Hospital for Sick Children. Families unable to attend were sent letters for their physicians that outlined testing and treatment recommendations and requested results to be forwarded to the Hospital for Sick Children. Others were referred to their local health unit for follow-up examination.

Most infants (79 of 107) were evaluated at the Hospital for Sick Children with physical examination, TST, liver function testing, and chest radiography, and medical histories were obtained. Infants were treated with isoniazid at a dosage of 15 mg/kg per day and pyridoxine at a dosage of 2 mg per day. One infant could not tolerate isoniazid and was given rifampin at a dosage of 10 mg/kg per day. Infants with abnormalities on chest radiographs were admitted for performance of 3 rounds of gastric aspiration and thoracic CT scanning. Infants were evaluated 1 month later (i.e., ∼3 months after exposure) and again at 3 months after their expected date of delivery (i.e., at a corrected age of 3 months). Treatment was continued until the final evaluation and stopped if TST results were negative for M. tuberculosis at that time.

All microbiological testing was done at the Ontario Provincial Health Laboratory, according to standard procedures [22]. M. tuberculosis was identified by the Accuprobe test (Gen-Probe; California). Amplification detection of rRNA from M. tuberculosis was performed directly on specimens using a nucleic acid amplification assay. Restriction fragment-length polymorphism (RFLP) typing analysis was performed using the international reference method [23]. Spoligotyping analysis was based on the detection and analysis of the spacer elements in the M. tuberculosis genome's direct repeat region [24].

Results. The mother of patient 1 had positive TST results (induration 16 mm in diameter). Sputum and uterine biopsy specimens were positive for M. tuberculosis by nucleic acid amplification assay and culture. The isolates of M. tuberculosis from patient 1, his mother, and patient 2 were very closely related by RFLP (91% genotypic identity by dendrogram analysis) and identical by spoligotyping (figure 2), confirming nosocomial transmission. All 3 siblings had negative TST results.

Figure 2
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Figure 2

Restriction fragment-length polymorphism analysis (RFLP) (A) and spoligotyping analysis of isolates from patient 1, his mother, and patient 2, and reference (control) strains. BCG, bacille Calmette-Guerin; M. bovis, Mycobacterium bovis; M. tuberculosis, Mycobacterium tuberculosis.

The parents of patient 2 had negative baseline TST results for M. tuberculosis and normal chest radiograph findings; however, both had positive TST results 3 months later (indurations of 16 and 22 mm). Treatment with isoniazid was initiated.

Nine of the 328 health care workers identified as contacts of patient 1 had worked in the infant's room. Two (0.6%) of the health care workers were noncompliant with follow-up examination. Three (0.9%) had newly positive TST results (2 nurses who provided direct care for patient 1 and a unit clerk) and normal chest radiograph findings. They were referred for treatment for latent tuberculosis infection. No family members or visitors were found to have active tuberculosis.

The 2 patients were located in nonadjacent multi-bed rooms along the same corridor in the neonatal ICU. The ventilation system has a dedicated supply and exhaust with 6–9 air exchanges per hour. The filtration system is 95% effective in removing particles that are at least 1 micron in size. No shutdowns occurred on the days 19–26 January. The engineering review indicated that the transmission of M. tuberculosis particles by back-flow of the air exhaust was very unlikely.

Chart review revealed that both infants were in incubators, intubated, and ventilated. Patient 1 required frequent ventilatory manipulations toward the end of life. Reprocessing of respiratory equipment was done manually in the neonatal ICU by patient service aides. Instructions for cleaning and disinfection were scant, and used equipment was not consistently segregated, leading to the possibility of reusing a contaminated device. Therefore, inadequate disinfection of respiratory equipment was likely responsible for M. tuberculosis transmission from patient 1 to patient 2. No other infant had evidence of latent or active tuberculosis, and no neonatal ICU death was attributed to tuberculosis.

Discussion. Inadequately disinfected respiratory equipment was likely responsible for nosocomial transmission of tuberculosis from a congenitally infected infant to another infant in our neonatal ICU. This conclusion is supported by the presence of a normally functioning ventilation system, absence of other infected neonates, and absence of adults (apart from the mother of patient 1) with active infection. Inadequately reprocessed bronchoscopy and anesthesia equipment has been described as sources of tuberculosis transmission, as has the reuse of improperly disinfected feeding tubes [25–29].

Medical equipment that has been in contact with mucous membranes requires thorough cleaning followed by high-level disinfection [30–31]. In the cases we describe, a review of the disinfection procedures revealed a number of deficiencies, identifying several pieces of equipment which might have been shared between the infants. Modifications to reprocessing procedures resulting from this investigation included centralization of the hospital's reprocessing system, checks to ensure there were protocols for reprocessing all reusable equipment, and development of tracking systems for clinical equipment.

There is no standard approach for dealing with hospitalized infants who are potentially exposed to an infant with congenital tuberculosis [8–10, 19–20, 32–34]. We based our approach on a consensus opinion held by several experts on pediatric infectious diseases and tuberculosis, treating all potentially exposed infants until they had negative TST results at a corrected age of 3 months and had no signs, symptoms, or chest-radiograph evidence of tuberculosis. Although the age at which a TST becomes an accurate screen for tuberculosis infection in infants is unknown, we chose to stop prophylaxis at a corrected age of 3 months (minimum 3 months after exposure), which is consistent with current recommendations [35].

Transmission of tuberculosis from infants to health care workers has been reported and is likely related to aerosolization of bacilli during respiratory manipulations [8–10, 19–20, 36–37]. Patient 1 required frequent manipulations and high frequency-oscillation ventilation, a recognized risk factor [10]. Current recommendations state that most children with tuberculosis disease are not contagious and require only standard isolation precautions [35]. Airborne precautions are recommended for children with cavitary pulmonary tuberculosis, sputum smears positive for acid-fast bacilli, laryngeal involvement, or extensive pulmonary infection. Infants suspected of having congenital tuberculosis have recently been added to this list.

This case of indirect infant-to-infant transmission of tuberculosis underscores the need for appropriate infection control precautions if the diagnosis of congenital tuberculosis is suspected. Given the increasing number of immigrants to North America from countries where tuberculosis is endemic and imposes a high burden [38], a high index of suspicion for congenital tuberculosis must be maintained for ill neonates born to women at risk for tuberculosis.

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Acknowledgments

We wish to acknowledge the hard work and dedication of the Outbreak Investigation Team, which included the following persons: Dr. Stanley Read, Dr. Upton Allen, Dr. Anne Opavsky, Georgina MacDougall, Debra Louch (Division of Infectious Diseases, Hospital for Sick Children [HSC]), Carol Goldman, Laurie Streitenburger, Rick Wray, Renee Freedman (Infection Control, HSC), Margaret Roscoe (Division of Microbiology, HSC), Joy McGuire (Occupational Health Department, HSC), Donna Carr (Neonatal Intensive Care Unit, HSC), Julie Jeffrey (Division of Pediatric Medicine, HSC), Dr. David Manson (Radiology, HSC), Dr. Rob Stirling, Marg Mulholland (Toronto Public Health), Dr. Barbara Kawa (Ontario Public Health), Daniel Bolduc (Health Canada), Janice Campbell (Quality Management, HSC), Cyndy De Giusti, Helen Simeon (Public Affairs, HSC), Mary Jo Haddad (Administration, HSC), Anne Maki, Dr. George Broukhanski, Pam Chedore (Laboratories Branch, Ontario Ministry of Health and Long-Term Care).

Potential conflicts of interest. All authors: no conflicts.

  • Received April 1, 2004.
  • Accepted July 23, 2004.
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References

  1. ↵
    1. Snider DE,
    2. Bloch AB
    . Congenital tuberculosis. Tubercle 1984;65:81-2.
    CrossRefMedlineWeb of Science
    1. Cantwell MF,
    2. Shehab ZM,
    3. Costello AM,
    4. et al
    . Congenital tuberculosis. N Engl J Med 1994;330:1051-4.
    CrossRefMedlineWeb of Science
    1. Adhikari M,
    2. Pillay T,
    3. Pillay DG
    . Tuberculosis in the newborn: an emerging disease. Pediatr Infect Dis J 1997;16:1108-12.
    CrossRefMedlineWeb of Science
    1. Manji KP,
    2. Msemo G,
    3. Tamim B,
    4. Thomas E
    . Tuberculosis (presumed congenital) in a neonatal unit in Dar-es-Salaam, Tanzania. J Trop Pediatr 2001;47:153-5.
    Abstract/FREE Full Text
    1. Sood M,
    2. Trehan A,
    3. Arora S,
    4. Jayashanker K,
    5. Marwaha RK
    . Congenital tuberculosis manifesting as cutaneous disease. Pediatr Infect Dis J 2000;19:1109-11.
    CrossRefMedlineWeb of Science
    1. Mazade MA,
    2. Evans EM,
    3. Starke JR,
    4. Correa AG
    . Congenital tuberculosis presenting as sepsis syndrome: case report and review of the literature. Pediatr Infect Dis J 2001;20:439-42.
    CrossRefMedlineWeb of Science
    1. Senbil N,
    2. Sahin F,
    3. Caglar MK,
    4. Oksal A,
    5. Yilmaz F,
    6. Tuna F
    . Congenital tuberculosis of the ear and parotid gland. Pediatr Infect Dis J 1997;16:1090-1.
    CrossRefMedlineWeb of Science
  8. ↵
    1. Lee LH,
    2. LeVea CM,
    3. Graman PS
    . Congenital tuberculosis in a neonatal intensive care unit: case report, epidemiological investigation, and management of exposures. Clin Infect Dis 1998;27:474-7.
    Abstract/FREE Full Text
    1. Saitoh M,
    2. Ichiba H,
    3. Fujioka H,
    4. Shintaku H,
    5. Yamano T
    . Connatal tuberculosis in an extremely low birth weight infant: case report and management of exposure to tuberculosis in a neonatal intensive care unit. Eur J Pediatr 2001;160:88-90.
    CrossRefMedlineWeb of Science
  10. ↵
    1. Laartz BW,
    2. Narvarte HJ,
    3. Holt D,
    4. Larkin JA,
    5. Pomputius WF
    . Congenital tuberculosis and management of exposures in a neonatal intensive care unit. Infection Control and Hospital Epidemiology 2002;23:573-9.
    CrossRefMedlineWeb of Science
    1. Balasubramanian S,
    2. Shivram R,
    3. Padmasani LN,
    4. Nagaraju
    . Congenital tuberculosis. Indian J Pediatr 1999;66:148-50.
    CrossRefMedline
    1. Pillay T,
    2. Adhikari M
    . Congenital tuberculosis in a neonatal intensive care unit. Clin Infect Dis 1999;29:467-8.
    CrossRefMedlineWeb of Science
    1. Ray M,
    2. Dixit A,
    3. Vaipei K,
    4. Singhi PD
    . Congenital tuberculosis. Indian Pediatrics 2002;39:1167-8.
    Medline
    1. Kobayashi K,
    2. Haruta T,
    3. Maeda H,
    4. Kubota M,
    5. Nishio T
    . Cerebral hemorrhage associated with vitamin K deficiency in congenital tuberculosis treated with isoniazid and rifampin. Pediatr Infect Dis J 2002;21:1088-90.
    CrossRefMedlineWeb of Science
    1. Pejham S,
    2. Altman R,
    3. Li KI,
    4. Munoz JL
    . Congenital tuberculosis with facial nerve palsy. Pediatr Infect Dis J 2002;21:1085-6.
    CrossRefMedlineWeb of Science
    1. Chou YH
    . Congenital tuberculosis proven by percutaneous liver biopsy: report of a case. J Perinat Med 2002;30:423-5.
    CrossRefMedlineWeb of Science
    1. Hatzistamatiou Z,
    2. Kaleyias J,
    3. Ikonomidou U,
    4. Papathoma E,
    5. Prifti E,
    6. Kostalos C
    . Congenital tuberculous lymphadenitis in a preterm infant in Greece. Acta Paediatr 2003;92:392-4.
    CrossRefMedlineWeb of Science
    1. Abughali N,
    2. Van Der Kuyp F,
    3. Annable W,
    4. Kumar ML
    . Congenital tuberculosis. Pediatr Infect Dis J 1994;13:738-41.
    MedlineWeb of Science
  19. ↵
    1. Machin GA,
    2. Fanning EA,
    3. Molesky M
    . Perinatally acquired neonatal tuberculosis: report of two cases. Pediatric Pathology 1992;12:707-16.
    CrossRefMedlineWeb of Science
  20. ↵
    1. Myers JP,
    2. Perlstein PH,
    3. Light IJ,
    4. Towbin RB
    . Tuberculosis in pregnancy with fatal congenital infection. Pediatrics 1981;67:89-94.
    Abstract/FREE Full Text
  21. ↵
    1. Long R
    , editor. Canadian tuberculosis standards. 5th ed. Ottawa: Canadian Lung Association and Government of Canada; 2000.
  22. ↵
    1. Murray PR
    1. Pfyffer GE,
    2. Brown-Elliott BA,
    3. Wallace RJ Jr
    . Mycobacterium: general characteristics, isolation, and staining procedures. In: Murray PR, editor. Manual of clinical microbiology. 8th ed. Washington, DC: ASM Press; 2003. p. 532-59.
  23. ↵
    1. van Embden JD,
    2. Cave MD,
    3. Crawford JT,
    4. et al
    . Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology. J Clin Microbiol 1993;31:406-9.
    Abstract/FREE Full Text
  24. ↵
    1. Kamerbeek J,
    2. Schouls L,
    3. Kolk A,
    4. et al
    . Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. J Clin Microbiol 1997;35:907-14.
    Abstract/FREE Full Text
  25. ↵
    1. Ramsey AH,
    2. Oemig TV,
    3. Davis JP,
    4. et al
    . An outbreak of bronchoscopy-related Mycobacterium tuberculosis infections due to lack of bronchoscope leak testing. Chest 2002;121:976-81.
    Abstract/FREE Full Text
    1. Agerton T,
    2. Valway S,
    3. Gore B,
    4. et al
    . Transmission of a highly drug-resistant strain (strain W1) of Mycobacterium tuberculosis. Community outbreak and nosocomial transmission via a contaminated bronchoscope. JAMA 1997;278:1073-7.
    Abstract/FREE Full Text
    1. Southwick KL,
    2. Hoffmann K,
    3. Ferree K,
    4. et al
    . Cluster of tuberculosis cases in North Carolina: possible association with atomizer reuse. Am J Infect Control 2001;29:1-6.
    CrossRefMedlineWeb of Science
    1. Langevin PB,
    2. Rand KH,
    3. Layon AJ
    . The potential for dissemination of Mycobacterium tuberculosis through the anesthesia breathing circuit. Chest 1999;115:1107-14.
    Abstract/FREE Full Text
  29. ↵
    1. Mihailescu P,
    2. Calciu B,
    3. Ionescu J
    . [Epidemic of tuberculosis in a maternity hospital triggered by congenital tuberculosis in a newborn infant]. Rev Ig Bacteriol Virusol Parazitol Epidemiol Pneumoftiziol Pneumoftiziol 1979;28:85-93.
    Medline
  30. ↵
    1. Health Canada
    . Infection control guidelines. Hand washing, cleaning, disinfection and sterilization in health care. Ottawa: Health Canada; 1998.
  31. ↵
    1. Health Canada
    . Guidelines for preventing the transmission of tuberculosis in Canadian health care facilities and other institutional settings. Can Commun Dis Rep 1996;22(Suppl 1):1-50.
    Medline
  32. ↵
    1. Light IJ,
    2. Saidleman,
    3. Sutherland JM
    . Management of newborns after nursery exposure to tuberculosis. Am Rev of Resp Dis 1974;109:415-9.
    1. Steiner P,
    2. Rao M,
    3. Victoria MS,
    4. Rudolph N,
    5. Buynoski G
    . Miliary tuberculosis in two infants after nursery exposure: epidemiologic, clinical, and laboratory findings. Am Rev Resp Dis 1976;113:267-71.
    MedlineWeb of Science
  34. ↵
    1. Nivin B,
    2. Nicholas P,
    3. Gayer M,
    4. Frieden TR,
    5. Fujiwara PI
    . A continuing outbreak of multidrug-resistant tuberculosis, with transmission in a hospital nursery. Clin Infect Dis 1998;26:303-7.
    Abstract/FREE Full Text
  35. ↵
    1. Pickering LK
    1. American Academy of Pediatrics
    . Tuberculosis. In: Pickering LK, editor. Red book: 2003 report of the committee on infectious diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003. p. 642-60.
  36. ↵
    1. Rabalais G,
    2. Adams G,
    3. Stover B
    . PPD skin test conversion in health-care workers after exposure to Mycobacterium tuberculosis infection in infants. Lancet 1991;338:826.
    MedlineWeb of Science
  37. ↵
    1. Stewart CJ
    . Tuberculosis infection in a paediatric department. BMJ 1976;1:30-2.
    Abstract/FREE Full Text
  38. ↵
    1. Talbot EA,
    2. Moore M,
    3. McCray E,
    4. Binkin NJ
    . Tuberculosis among foreign-born persons in the United States, 1993–1998. JAMA 2000;284:2894-900.
    Abstract/FREE Full Text
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  1. Clin Infect Dis. (2004) 39 (11): 1719-1723. doi: 10.1086/425740
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