CDC Reviews Evaluation of People Who May Have Been Exposed to the Recent XDR-TB Case

June 20, 2007 — In a teleconference June 19, the US Centers for Disease Control and Prevention (CDC) presented guidelines reviewing the evaluation of people who might have been exposed to the recent case of extensively drug-resistant pulmonary tuberculosis (XDR-TB). The new guidelines, which are summarized in algorithms on the CDC website, address the management of people with a positive QuantiFERON-TB Gold (QFT-G) or tuberculin skin test (TST).
In May 2007, a person with recently diagnosed, culture-confirmed XDR-TB traveled on the following 2 extended flights, each lasting more than 8 hours: Air France #385/Delta #8517 on May 12 from Atlanta, Georgia, to Paris, France; and Czech Air #0104 on May 24 from Prague, Czech Republic, to Montreal, Quebec. Since May 25, this person has been hospitalized in airborne isolation.
For the purpose of this XDR-TB contact investigation, all US residents and citizens who were on these flights are considered to be contacts of the XDR-TB patient. For people identifying themselves as passengers on one of these flights, the CDC requests that the physicians they contact perform TB evaluation and testing or refer the passenger to the appropriate state or local TB control office for TB testing, evaluation, and follow-up.
Theresa Harrington, MD, a medical officer with the United States Public Health Service and medical epidemiologist with the CDC's Division of TB Elimination Outbreak Investigation Team, noted that the purpose of the teleconference was not to discuss the specifics of this XDR-TB case or subsequent investigation, but rather to address guidelines for the clinical evaluation and management of individuals exposed or potentially exposed to XDR-TB.
She also pointed out that it is the physician's responsibility to determine whether or not the patient is truly a contact of the index case, and not just a member of the worried well who might be unduly concerned about casual or distant contact not likely to constitute true exposure. Passengers on the same plane, healthcare workers who examined or treated the patient, and household or family contacts of the index patient are considered to be actual contacts.
"Among persons who are infected with Mycobacterium tuberculosis (i.e., latent tuberculosis infection), it can take 8 to 10 weeks [after] exposure [before] the TST result or QFT-G [test] becomes positive," Dr. Harrington said. "A first-round TST or QFT-G [test], not both, should be performed as soon as possible following exposure to the XDR-TB patient. If the first round of symptom screening and TST or QFT-G result is negative, a second TB evaluation and TST or QFT-G [test should be] performed 8 to 10 weeks [after] the last known exposure to the XDR-TB patient (i.e., round 2 testing)."
Dr. Harrington noted that the second round of TB evaluation and testing is required because a negative TST or QFT-G result obtained less than 8 weeks after exposure can be unreliable in excluding latent tuberculosis infection (LTBI).
For the purpose of a contact investigation, a positive TST result is defined as an induration of 5 mm or more for any contact. Although people with a previous documented positive TST or QFT-G result or with previously diagnosed TB disease do not need to be retested, these people should still undergo TB evaluation, which should include a complete history, signs and symptoms screening, and chest X-ray.
Past medical-history evaluation should document any illness that increases the risk of latent TB progressing to TB, such as HIV infection, cancer, immunocompromised state, renal failure, or even uncontrolled diabetes mellitus. If patients at high risk for HIV infection are not aware of their HIV status, HIV counseling and testing should be offered. Other important points to cover in the medical history are any previous treatment for TB, having been part of a TB investigation, past TST results, immigration from a TB-endemic area, or having received a Bacille Calmette-Guérin (BCG) vaccination. Social or behavioral risk factors for LTBI include incarceration and illicit drug use.
Symptoms suggestive of active TB include fever, chills, night sweats, productive cough, and unexplained weight loss. Signs of active TB that should arouse suspicion on physical examination include cachectic habitus, chronically ill appearance, cough, and pulmonary findings.
If the medical evaluation suggests active TB, a chest X-ray should be performed immediately, with airborne isolation for the patient if the X-ray is positive, as well as sputum smear for acid-fast staining and sputum culture and evaluation by a TB expert.
"Consultation with a TB expert, especially one with experience managing [multidrug-resistant] or XDR-TB, is strongly recommended," Dr. Harrington said. "This is recommended especially for any contact suspected of having active TB disease who has a positive TST or QFT-G result or who is immunocompromised, regardless of TST or QFT-G result."
If there is no evidence of active TB and the initial TB test is negative, the TB test should be repeated 8 to 10 weeks later. No further evaluation is necessary if the second test is negative and the patient is not immunocompromised. However, if the second round TB test is positive, this should be considered a new conversion.
Physicians administering a TST or QFT-G test should document the date, the spot where the test is placed, the lot number, the expiration date, and the antigen used. The test should be read 48 hours later and size (in mm) of the induration should be recorded for TST; if positive, a chest X-ray should be performed. If there are signs and symptoms of active TB, chest X-ray and sputum for smear and culture are warranted.
A TST or QFT-G test can be used in people who have a history of BCG vaccination; in these people, a TST result of 5 mm induration or more is considered to be positive, warranting further TB evaluation and testing.
A nonimmunocompromised patient with a positive TB test, either TST or QFT-G, can be considered to have been infected, either in the past or recently. If not previously treated, these patients should receive standard LTBI treatment with 5 months of isoniazid. If the TB test is positive but there is no other evidence suggesting infection, a TB expert should be consulted. Follow-up symptom screening and chest X-ray should be performed at 3, 6, 12, 18, and 24 months, because the risk of developing active TB from LTBI is highest during the first 2 years.
"The risk of progressing to TB disease from LTBI is approximately 10% over a lifetime in a person with a normal immune system, or 5% within the first 2 years following infection, and that's why we want to follow them particularly closely with symptom screening and chest radiograph for those first 2 years," Dr. Harrington said.
Contacts who are immunocompromised, for example because of HIV infection, AIDS, use of corticosteroids, or tumor necrosis factor-alpha treatment, should have a medical evaluation and chest X-ray immediately. However, these patients do not always have infiltrates on chest X-ray. If there is no evidence suggesting active TB, and the initial TST or QFT-G test is negative, the test should be repeated 8 to 10 weeks after the last exposure to the index patient. If the test is still negative after the second round, follow-up symptom screening and chest X-ray should be performed at 3, 6, 12, 18, and 24 months. If the initial or second-round test is positive, further management is warranted.
For immunocompromised contacts with a positive TST or QFT-G test, past medical history should be reviewed for other risk factors, such as previous TB exposure, birth in a country with a high TB burden, previous TB or LTBI, and/or previous exposure to a TB contact. If any of these risk factors are present, a positive TST or QFT-G test probably suggests TB infection in the past, not from the index patient. Isoniazid treatment for 9 months can be considered for LTBI if the patient was not previously treated.
If it is unclear whether or not the positive test result in the above scenario resulted from exposure to the XDR-TB index case, a TB expert should be consulted. Standard therapy suffices if the patient was exposed to someone infected with a normal-resistance TB organism. However, the lack of available agents to treat XDR-TB mandates consultation with a TB expert for those thought to be infected from exposure to the XDR-TB index case.
"At least at this point, we're not expecting that there has been a lot of transmission from this case," Dr. Harrington said. "If you do find a person that you really think became infected from the XDR-TB patient, there is no standard therapy. We do not yet have enough world experience with XDR-TB, and there are very few medications that can be offered to somebody for treatment of disease, which is separate from treatment for latent TB infection."
Lauren Lambert, MD, a CDC expert on hospital transmission of TB, briefly addressed the evaluation of healthcare workers with possible exposure to an index case.
"Many of the guidelines [in place to protect] healthcare workers from infection resulting from exposure to TB are not evidence-based, but are based on expert opinion because there are a lack of available data," Dr. Lambert said. "So, for example, although the guidelines state that healthcare workers should be tested periodically, there is no real evidence to suggest what 'periodically' really means. It's a very gray area."