IDCR - Infectious Diseases in Corrections Report

Case Studies in the Treatment of Tuberculosis in the Correctional Setting

Edward M. Gardner, MD
Assistant Professor of Medicine
Division of Infectious Diseases
Denver Public Health & University of Colorado Health Sciences Center

Robert Belknap, MD
Instructor of Medicine
Division of Infectious Diseases
Denver Public Health & University of Colorado Health Sciences Center

Disclosures: Nothing to Disclose

Case 1: DA 28 year-old male was brought to a jail medical facility after being arrested for assault. He was intoxicated and complained of chest pain, cough, and night sweats intermittently for several weeks prompting the Sheriff's Deputy to alert the facility nurse. He had no significant past medical history, was born in Mexico and had been living in the United States for the past three years. His vital signs and physical exam were normal except for a heart rate of 120 beats per minute. A chest radiograph showed a faint left upper lobe fibronodular opacity.

Question: Based on his presentation the patient was placed in respiratory isolation. What should you do next?

Discussion: Diagnosing tuberculosis (TB) is challenging because the symptoms are often nonspecific and varied. The critical first step involves considering TB in the differential diagnosis for a broad range of symptoms. Approximately half of all TB cases admitted to the hospital have a delay in diagnosis primarily because TB is not initially considered.^1,2

The next step is to evaluate the patient's risk factors for 1) latent TB infection and 2) TB disease. In the U.S., the most common risk factor for infection is birth or residence in a high prevalence country (essentially anywhere other than North America, Western Europe, Australia or New Zealand). Other risks for infection include work or residence in a correctional facility, nursing home, or other congregate setting, current or prior homelessness, and substance abuse. Common risks for progression to TB disease include HIV-infection, other immunosuppressive illnesses or medications, diabetes, chronic renal failure, and scarring from prior TB on chest radiograph.

All suspect patients should have a chest radiograph performed. Remember that the chest radiograph cannot always differentiate between active TB and old scarring. Once TB is suspected, the patient should be placed in respiratory isolation until it is determined if the patient has infectious pulmonary TB or an alternative diagnosis is made. All suspected or confirmed TB cases should be promptly reported to the department of health. In correctional settings without availability of airborne infection isolation rooms, evaluation of suspect cases may require hospital admission.

Along with the chest radiograph, assessment for active TB involves collecting three sputum smears and cultures, and placing a tuberculin skin test (TST) or performing a quantiferon test. These screening tools are helpful when positive by confirming that the patient was infected with M. tuberculosis at some time in their life. Alone the TST or quantiferon test cannot distinguish between TB disease and latent TB infection. Both of these tests can produce false negative results in as many as 25% of people with TB disease.³

Sputum smears and cultures are an important part of an initial evaluation for pulmonary TB. Traditionally, sputum samples have been collected on three successive mornings but some have suggested samples collected 8 hours apart with at least one early morning specimen may be adequate and shorten the time needed to collect these diagnostic tests.^4,5 Unfortunately, sputum smears have a poor sensitivity with only 50% of patients with pulmonary TB having a positive smear.3 While smear positive TB patients are the most infectious, patients who have smear negative pulmonary disease can also transmit M. tuberculosis.6 All suspect cases need to be followed closely while waiting for culture results and if released from incarceration, should be referred to the local health department for appropriate follow up.

In this case, the patient had a negative TST and three negative sputum smears. He was discharged from the hospital on azithromycin and released on bail. Three weeks later, cultures of all three sputum specimens were positive. His only contact information turned out to be a center for alcohol treatment where he hadn't been since his arrest. This highlights the importance of collecting extensive contact information from patients, such as this one, who had suspected TB. Information about family members and friends who may know where the patient is located can be obtained from the patient prior to release. In addition, reporting the suspected case to the local department of health, in accordance with local procedures, can be an important element in post-release follow-up. This patient was finally found a month later when he returned to the treatment center and learned the TB clinic was looking for him. He had an HIV antibody test performed and this was negative.

He was started on four-drug TB therapy until drug sensitivities were able to be completed. A repeat TST while on treatment was strongly positive which is not uncommon. Two months later his organism was found to be sensitive to isoniazid and rifampin, his remaining treatment was simplified to these antibiotics, and he was continued on directly observed therapy.

Case 2: A 29 year-old Hispanic male was referred to the hospital from the state prison with postprandial abdominal pain for several months that had acutely worsened over the past week and was associated with nausea, vomiting and fevers. He was born in Honduras, had lived in the U.S. for 10 years and had been incarcerated for six months. An ultrasound showed a thickened gall bladder and dilated extra-hepatic biliary ducts. He was diagnosed with cholecystitis and initially treated with intravenous levofloxacin and metronidazole. He improved clinically and was discharged to the prison infirmary on intravenous ticarcillin/clavulanate, but returned to the hospital three days later for increasing pain and fevers.

Question: What should you do next?

Discussion: During the initial infection with TB, the bacilli replicate in the alveoli, enter the lymphatics and bloodstream, and disseminate throughout the body. For most people, the immune system contains the infection through the formation of granulomas. Only about 5-10% of persons infected will progress to active TB during their lifetime with 80 - 85% of these patients having pulmonary TB and 15 - 20% having extrapulmonary TB.³

The most common extrapulmonary sites in descending order of frequency are lymphatic, pleural, bone and joint, meningeal, peritoneal, genitourinary, and then other sites.³ The presenting signs and symptoms depend on the location of disease but may include more typical symptoms such as fever, night sweats, and weight loss. Importantly, some patients presenting with extrapulmonary symptoms will have active pulmonary TB as well. The occurrence of active disease at multiple sites is more common in immunocompromised patients, particularly those with advanced HIV infection. All patients being evaluated for extrapulmonary TB should have a chest radiograph due to the risk for occult pulmonary TB with the potential for airborne transmission to others.

While diagnosing pulmonary TB can be challenging (Case 1), diagnosing extrapulmonary disease can be even more difficult. As with pulmonary TB, the key to a timely diagnosis requires consideration of TB in the differential diagnosis. Many sites, like pleural, peritoneal, meningeal, and pericardial, are associated with a very low organism burden. Therefore, smears are rarely positive and cultures of fluid are less than 50% sensitive. Nucleic acid amplification tests were developed in part to address this limitation and are highly specific but unfortunately lack sufficient sensitivity to assume a negative test excludes the diagnosis. ⁷ Therefore, definitive diagnosis of extrapulmonary TB often requires a tissue sample for pathology and culture.

Delays in diagnosis of pulmonary and extra-pulmonary TB can be increased by the empiric use of fluoroquinolones. Many fluoroquinolones are active against Mycobacterium tuberculosis and some are under investigation as first line agents in combination therapy. ^8,9 Because patients can have a profound clinical response, clinicians may be fooled into a false sense of security since treatment with fluoroquinolones can temporarily lead to suppression of organism growth in cultures. As with any other single agent, treatment with a fluoroquinolone will not cure TB, and patients will relapse, often soon after stopping therapy.

TMC-125 would be another agent that may provide some antiretroviral activity. The activity of TMC-125 is diminished as NNRTI mutations accumulate, therefore, if she harbors additional mutations - acquired during her treatment with efavirenz but not sufficiently present now to be detected - this drug may be less useful.

In our patient, a biliary drain was placed for symptom relief and plans made for surgical exploration. Prior to surgery, samples of his biliary fluid and stool were sent to microbiology, where an AFB smear was positive, and eventually grew M. tuberculosis. His clinical response during the first hospitalization was thought to be from the levofloxacin he received, but his symptoms quickly returned when he was switched to an antibiotic without activity against M. tuberculosis. He was started on standard four drug TB therapy with isoniazid, rifampin, pyrazinamide, and ethambutol. An HIV test was performed and was positive. The patient's CD4 cell count was 237/mm3 and it was decided to defer initiation of HIV therapy for approximately three to six months when there may be reduced risk of immune reconstitution reaction. When concomitantly administered, HIV and anti-tuberculous therapy have to be carefully selected to avoid drug-drug interactions (see IDCR February 2006 and this issue's TB 101 for a detailed discussion of antiretroviral and TB drug interactions).