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Guide to the Application of Genotyping to Tuberculosis Prevention and Control

Tuberculosis Genotyping Case Studies: How TB Programs Have Used Genotyping

A Misdiagnosis that Was Identified with Genotyping

A 36-year-old woman came to the emergency room with a 2-day history of fevers, cough, and right-sided pleuritic chest pain. She had no known history of tuberculosis exposure. Her past medical history was notable for injection drug use (heroin) up to the time of her admission. Her physical examination showed a fever of 39C and signs of consolidation at the right lung base. A chest radiograph showed right lower lobe infiltrates with an associated small pleural effusion. The patient was admitted to respiratory isolation and treated with intravenous ceftriaxone. She responded quickly and became afebrile after 2 days of therapy. A standard sputum culture grew normal oral flora; blood culture results were negative. Three sputum specimens were acid-fast bacilli (AFB) smear-negative, but she had a 15-mm response to tuberculin skin testing (TST). A human immunodeficiency virus (HIV) test was negative. She was discharged to complete 7 days of therapy with amoxicillin for community-acquired pneumonia.

She was called back to the TB Clinic 1 month after discharge when one of the three sputum specimens grew drug-susceptible M. tuberculosis, and she was given a diagnosis of tuberculosis. By that time she reported feeling back to normal, and a repeat chest radiograph was normal. Two additional sputum specimens were collected and were AFB smear- and eventually culture-negative. She was treated with isoniazid (INH), rifampin, pyrazinamide, and ethambutol for 2 months and then with isoniazid and rifampin for 4 additional months. The TB control program also performed a relatively large contact investigation. Two years later, during a study in which all M. tuberculosis isolates underwent genotyping, her isolate was found to match that of a specimen from a laboratory proficiency test specimen that underwent initial processing on the same day.

This case has several characteristic features of a false-positive culture result. First, and most importantly, the clinical case was atypical for tuberculosis with an acute onset and rapid resolution with antibiotic therapy having no activity against mycobacteria. Although the patient had latent tuberculosis (the positive tuberculin skin test), the fact that the infiltrate completely resolved within 1 month, essentially without anti-tuberculosis therapy, is not consistent with tuberculosis. Second, only one of several specimens grew M. tuberculosis (a single-positive culture result). Routine review of single-positive culture results is one method to detect potential false-positive cultures. Treating this patient for TB required the TB program to use valuable resources and exposed the patient to the toxicity of unnecessary multidrug therapy.

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