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Transmission of Multidrug-resistant Tuberculosis Confirmed by Endobronchial Ultrasound Biopsy of a Mediastinal Lymph Node and DNA Fingerprinting Analysis

Lyu, Jiwon MD*; Kim, Chang Ki MD; Kim, Mi-Na MD; Choi, Chang-Min MD*; Kim, Woo Sung MD*; Kim, Dong Soon MD*; Shim, Tae Sun MD*

Journal of Bronchology & Interventional Pulmonology: October 2010 - Volume 17 - Issue 4 - p 345-347
doi: 10.1097/LBR.0b013e3181f1e7f1
Case Reports
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Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was recently introduced for sampling of mediastinal masses and nodes, for staging of lung cancer, and for diagnosing other benign diseases including tuberculosis (TB). However, EBUS-TBNA has not been used to date to confirm the presence of multidrug-resistant TB (MDR-TB). We here describe the diagnosis of MDR-TB of a mediastinal lymph node by EBUS biopsy. MDR-TB had been transmitted to our patient from her son who had pulmonary TB, and the diagnosis of MDR-TB was confirmed by a restriction fragment length polymorphism analysis of the IS6110 segment of Mycobacterium tuberculosis isolates. Our findings highlight the use of EBUS-TBNA in diagnosing TB, including MDR-TB, and malignancies, in a TB-endemic area.

*Division of Pulmonary and Critical Care Medicine

Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Medical Center

The Korean Institute of Tuberculosis, Seoul, Korea

Sources of financial support: We have no financial or any other conflict of interest regarding the contents of this manuscript.

Reprints: Tae Sun Shim, MD, Division of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Poongnap-dong, Songpa-gu, Seoul 138-736, South Korea (e-mail: shimts@amc.seoul.kr).

Received for publication March 6, 2010; accepted July 6, 2010

Institution at which the work was performed: Asan Medical Center.

Conflicts of Interest: No author has a conflict of interest to disclose.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has proven to be useful for lymph node staging in lung cancer patients1 and in diagnosing intrapulmonary and mediastinal tumors, hilar and/or mediastinal lymphadenopathy, and sarcoidosis.1–3 Recently, EBUS-TBNA has been used in the rapid diagnosis of tuberculosis (TB), increasing the diagnostic yield.4 To date, however, EBUS-TBNA has not been used for the diagnosis of multidrug-resistant TB (MDR-TB). We here use EBUS-TBNA, together with restriction fragment length polymorphism (RFLP) analysis of Mycobacterium tuberculosis isolates, to diagnose MDR-TB, including transmission between family members.

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CASE REPORT

Patient 1 (Index Case)

A 20-year-old bacille Calmette-Guérin--vaccinated male patient was hospitalized in April 2008 because of a 3-week history of cough and a 1-week history of blood-tinged sputum and fever. The patient had lost 4 kg of weight during the previous 4 months. There was no history of TB or other underlying disease. At admission, his body temperature was 38.2°C and his pulse rate was 125 beats/min; other parameters were normal. A chest radiograph showed multiple irregular centrilobular nodules in both the upper lobes. Microscopic examination of the sputum showed acid-fast bacilli (AFB). A tuberculin skin test and a human immunodeficiency virus test were negative. He was preliminarily diagnosed with pulmonary TB and in May 2008 he commenced treatment with isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and pyrazinamide (PZA). Two months later, a sputum culture was confirmed as positive for M. tuberculosis, and drug susceptibility testing (DST) showed that the isolate was resistant to INH, RMP, EMB, PZA, kanamycin, and prothionamide but susceptible to streptomycin (SM), p-aminosalicylic acid (PAS), cycloserine (CLOS), amikacin, and ofloxacin. In August 2008, the patient was switched to SM, levofloxacin, PAS, CLOS, and amoxicillin/clavulanate. In November 2008, his sputum culture was negative and he is still undergoing treatment as of January 2010.

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Patient 2 (Contact)

A 54-year-old bacille Calmette-Guérin--vaccinated female patient, mother of the index patient (patient 1) and living in the same house for a long period of time, visited our hospital for contact investigation in June 2008. Many years earlier, she had undergone a total thyroidectomy because of thyroid cancer, but she had no history of TB. As she had no symptoms suggestive of TB and her chest radiograph was normal, she was followed up without treatment. One year later, a routine computed tomography scan of her chest showed a newly developed, right-sided paratracheal lymphadenopathy, compared with an earlier computed tomography scan in 2005 (Fig. 1). She was negative for human immunodeficiency virus and routine bronchoscopy was unremarkable. EBUS-TBNA was performed using a bronchoscope (BF-UC260F-OL8; Olympus, Tokyo, Japan) (Fig. 2). The specimen was negative for AFB staining, but a culture was later positive for M. tuberculosis. On the basis of the DST pattern of the index patient, this patient was prescribed treatment with SM, moxifloxacin, PAS, CLOS, and amoxicillin/clavulanate in October 2009. DST of her isolate showed resistance to INH, RMP, EMB, PZA, and prothionamide. RFLP analysis showed that the isolates from both the patients had identical band patterns, confirming the transmission of MDR-TB between family members (ie, from the son to his mother) (Fig. 3).

FIGURE 1.

FIGURE 1.

FIGURE 2.

FIGURE 2.

FIGURE 3.

FIGURE 3.

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DISCUSSION

To the best of our knowledge, this is the first instance in which EBUS-TBNA was used to confirm MDR-TB, indicating the use of this technique in diagnosing both TB and malignancies, in a TB-endemic area.

Of our 2 patients, the son was first diagnosed with pulmonary MDR-TB and his mother was later diagnosed with TB lymphadenopathy. The DST results of the 2 isolates were almost identical, and both the isolates showed the same RFLP profile of the IS6110 segment, confirming the transmission of MDR-TB between family members. Although TB is often transmitted from parents to children within a family,5 our finding was the reverse, in that TB had been transmitted from the son to the mother. Neither the mother nor other family members had a history of TB, and the mother's TB was not infectious, indicating that the son was the index patient.

EBUS-TBNA has proven useful for sampling mediastinal masses and nodes and for staging of lung cancer, as well as in the diagnosis of sarcoidosis, lymphoma, and, more recently, TB.1–4 Given the higher diagnostic yield of EBUS-TBNA over conventional blind TBNA in patients with mediastinal lymph nodes except subcarinal nodes6 and relatively small lymph node size in this case, EBUS-TBNA was preferred to conventional TBNA in this case.

On account of the relative safety of the technique and the high diagnostic yield, EBUS-TBNA should be used to sample accessible lymph nodes and masses, and the specimens obtained should be cultured and stained for AFB, especially in TB-endemic areas.

In conclusion, we used EBUS-TBNA to confirm MDR-TB mediastinal lymphadenopathy transmitted from the son to the mother. EBUS-TBNA may play a significant role in diagnosing TB in TB-endemic areas.

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REFERENCES

1. Gu P, Zhao YZ, Jiang LY, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for staging of lung cancer: a systematic review and meta-analysis. Eur J Cancer. 2009;45:1389–1396.
2. Yasufuku K, Chiyo M, Sekine Y, et al. Real-time endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal and hilar lymph nodes. Chest. 2004;126:122–128.
3. Nakajima T, Yasufuku K, Kurosu K, et al. The role of EBUS-TBNA for the diagnosis of sarcoidosis: comparisons with other bronchoscopic diagnostic modalities. Respir Med. 2009;103:1796–1800.
4. Lin SM, Chung FT, Huang CD, et al. Diagnostic value of endobronchial ultrasonography for pulmonary tuberculosis. J Thorac Cardiovasc Surg. 2009;138:179–184.
5. Moss W. Tuberculosis in the home: contact history and childhood tuberculosis in central Harlem. Clin Pediatr (Phila). 1998;37:753–755.
6. Herth F, Becker HD, Emst A. Conventional vs endobronchial untrasound-guided transbronchial needle aspiration: a randomized trial. Chest. 2004;125:322–325.
Keywords:

tuberculosis; multidrug resistant; bronchoscopy; endobronchial ultrasound; disease transmission; infectious; polymorphism; restriction fragment length

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