This is an official
CDC HEALTH ADVISORY

Distributed via Health Alert Network
Tuesday, May 29, 2007, 0:40 EDT (12:40 PM EDT)
CDCHAN-00261-2007-05-29-ADV-N

Investigation of U.S. Traveler with Extensively Drug Resistant Tuberculosis (XDR TB)

The Centers for Disease Control and Prevention (CDC) is working with a number of international, state, and local partners on an investigation involving a U.S. citizen recently diagnosed with extensively drug-resistant tuberculosis (XDR TB).  XDR TB has been recently defined as a subtype of multidrug-resistant tuberculosis (MDR TB) with additional resistance to the two most important second-line antibiotics (i.e., a fluoroquinolone and an injectable agent [amikacin, kanamycin, or capreomycin]) in addition to the two most important first-line drugs (i.e., isoniazid and rifampin).

CDC learned that a patient with XDR TB traveled to Europe via commercial airline (Air France # 385) departing Atlanta on May 12 and arriving in Paris on May 13, 2007, and returned to the United States after taking a commercial flight on May 24 from Prague, Czech Republic to Montreal, Canada (Czech Air # 410). The patient re-entered the U.S. on May 24 via automobile.  Since May 25, the patient has been hospitalized in respiratory isolation and is undergoing additional medical evaluation.

CDC is collaborating with U.S. state and local health departments, international Ministries of Health, the airline industry, and the World Health Organization (WHO) regarding appropriate notification and follow up of passengers and crew potentially at risk for exposure to XDR TB. Each country involved in the investigation is determining the most appropriate guidance for its residents. The following recommendations have been developed for U.S. residents who may have been exposed to this patient. 

This patient has radiographic evidence of pulmonary TB, is culture-positive for XDR TB, but is sputum smear negative for acid fast bacilli and is relatively asymptomatic.  On the basis of the patient’s clinical and laboratory status, and lack of receiving adequate treatment for XDR TB, this patient was considered potentially infectious at the time of his airline travel, and meets the criteria in the WHO guidelines for initiating an airline contact investigation.  http://whqlibdoc.who.int/hq/2006/WHO_HTM_TB_2006.363_eng.pdf  

In accordance with the WHO TB and Airline Travel Guidelines, to ensure appropriate follow-up and care for persons who may have been exposed to XDR TB, CDC is recommending the following for passengers and crew onboard Air France # 385 departing Atlanta on May 12 and arriving in Paris on May 13, and on Czech Air # 410 departing from Prague and arriving in Montreal on May 24: passengers seated in the same row as the index patient and those seated in the two rows ahead and the two rows behind, as well as the cabin crew members working in the same cabin should be evaluated for TB infection. This includes initial evaluation and testing with follow up  8-10 weeks later for re-evaluation.

As there has never been an airline contact investigation for XDR TB, it is not known if the current recommendations are adequate to determine the possible range and risk of transmission of infection. Because of the serious consequences of XDR TB and anticipated public concern, in addition to the contacts listed above, all U.S. residents and citizens on these flights should be notified and encouraged to seek TB testing and evaluation.  

Drug-susceptible (regular) TB and XDR TB are thought to be spread the same way.  TB bacilli become aerosolized when a person with TB disease of the lungs or throat coughs, sneezes, speaks, or sings. These bacilli can float in the air for several hours, depending on the environment.  Persons who breathe air containing these TB bacilli can become infected.  

The risk of acquiring any type of TB appears to depend on several factors, such as extent of disease in the source patient, duration of exposure, and ventilation.  Transmission has been documented in association with patients who have lung disease, and bacteria seen or cultured in sputum. Persons who become infected usually have been exposed for several hours (or days) in poorly ventilated or crowded environments. An important way to prevent the spread and transmission is by limiting an infectious person’s contact with other people.  Thus, people who have a confirmed diagnosis of TB or XDR TB are placed on treatment and kept isolated until they are no longer infectious.

Persons who believe they may have been exposed to TB or XDR TB can call 1-800 CDC INFO for further information.

Where to go for information about:  

Tuberculosis: http://www.cdc.gov/tb/default.htm

XDR TB: http://www.cdc.gov/tb/pubs/tbfactsheets/xdrtb.htm http://www.cdc.gov/tb/pubs/tbfactsheets/xdrtb.htm  and http://www.cdc.gov/tb/pubs/tbfactsheets/cdcandxdrtb.htm http://www.cdc.gov/tb/pubs/tbfactsheets/cdcandxdrtb.htm

TB Testing: http://www.cdc.gov/tb/pubs/tbfactsheets/skintesting.htm http://www.cdc.gov/tb/pubs/tbfactsheets/skintesting.htm and http://www.cdc.gov/tb/pubs/tbfactsheets/QFT.htm http://www.cdc.gov/tb/pubs/tbfactsheets/QFT.htm

Infection control: http://www.cdc.gov/tb/pubs/tbfactsheets/ichcs.htm http://www.cdc.gov/tb/pubs/tbfactsheets/ichcs.htm  and http://www.cdc.gov/tb/pubs/tbfactsheets/rphcs.htm http://www.cdc.gov/tb/pubs/tbfactsheets/rphcs.htm

Tuberculosis and Air Travel:

http://whqlibdoc.who.int/hq/2006/WHO_HTM_TB_2006.363_eng.pdf

##This Message was distributed to State and Local Health Officers, Public Information Officers, Epidemiologists, State Laboratory Directors, BT Coordinators and HAN Coordinators, as well as Public Health Associations and Clinician organizations##

Extensively Drug-Resistant Tuberculosis (XDR TB)
Posted: April 2007

What is XDR TB?

Extensively drug-resistant tuberculosis (XDR TB) is a relatively rare type of multidrug-resistant tuberculosis (MDR TB). It is resistant to almost all drugs used to treat TB, including the two best first-line drugs: isoniazid and rifampin. XDR TB is also resistant to the best second-line medications: fluoroquinolones and at least one of three injectable drugs (i.e., amikacin, kanamycin, or capreomycin).

How is XDR TB spread?

Drug-susceptible (regular) TB and XDR TB are spread the same way. TB germs are put into the air when a person with TB disease of the lungs or throat coughs, sneezes, speaks, or sings. These germs can float in the air for several hours, depending on the environment. Persons who breathe in the air containing these TB germs can become infected.

TB is not spread by

• shaking someone’s hand
• sharing food or drink
• touching bed linens or toilet seats
• sharing toothbrushes
• kissing
• smoking or sharing cigarettes

Why is XDR TB so serious?

Because XDR TB is resistant to the most powerful first-line and second-line drugs, patients are left with treatment options that are much less effective and often have worse treatment outcomes. XDR TB is of special concern for persons with HIV infection or other conditions that can weaken the immune system. These persons are more likely to develop TB disease once they are infected, and also have a higher risk of death once they develop TB disease.

Who is at risk for getting XDR TB?

Drug-resistant TB (MDR or XDR) is more common in people who:

• Do not take their TB medicine regularly
• Do not take all of their TB medicines as told by their doctor or nurse
• Develop active TB disease again, after having taken TB medicine in the past
• Come from areas of the world where drug-resistant TB is common
• Have spent time with someone known to have drug-resistant TB disease

How can I prevent myself from getting TB?

Avoid close contact or prolonged time with known TB patients in crowded, enclosed environments like clinics, hospitals, prisons, or homeless shelters.

Can the TB vaccine (BCG) help prevent XDR TB?

There is a vaccine for TB disease called Bacille Calmette-Guérin (BCG) . It is used in some countries to prevent severe forms of TB in children. However, BCG is not generally recommended in the United States because it has limited effectiveness for preventing TB in adults. The effect of BCG against XDR TB would likely be similar to the effect on drug-susceptible TB.

If I have regular (drug-susceptible) TB, how can I prevent getting drug-resistant TB?

The most important thing is for you to continue taking all your TB medicines exactly as prescribed. No doses should be missed and treatment should not be stopped early. You should tell your health care provider if you are having trouble taking the medications. If you plan to travel, make sure you have enough medicine to last while away.

Can XDR TB be treated and cured?

Yes, in some cases. Some TB control programs have shown that cure is possible for an estimated 30% of affected people. Successful outcomes depend greatly on the extent of the drug resistance, the severity of the disease, and whether the patient’s immune system is weakened.

What are the symptoms of XDR TB?

The general symptoms of TB disease include feelings of sickness or weakness, weight loss, fever, and night sweats. The symptoms of TB disease of the lungs may also include coughing, chest pain, and coughing up blood. Symptoms of TB disease in other parts of the body depend on the area affected. If you have these symptoms, you should contact your doctor or local health department.

What should I do if I have been around someone who has XDR TB?

If you think you have been exposed to someone with TB disease, you should contact your doctor or local health department about getting a TB skin test or the QuantiFERON®-TB Gold test (QFT-G), a blood test. And tell the doctor or nurse when you spent time with this person.

How long does it take to find out if you have XDR TB?

If TB bacteria are found in the sputum (phlegm), the diagnosis of TB can be made in a day or two, but this finding will not be able to distinguish between drug-susceptible (regular) TB and drug-resistant TB. To determine drug susceptibility, the bacteria need to be grown and tested in a laboratory. Final diagnosis for TB, and especially for XDR TB, may take from 6 to 16 weeks.

Is XDR TB a problem in the United States?

The risk of acquiring XDR TB in the United States appears to be relatively low. However, it is important to acknowledge the ease at which TB can spread. As long as XDR TB exists, the United States is at risk and must address the threat.

How many cases of XDR TB have been reported in the United States?

In the United States, 49 cases of XDR TB have been reported between 1993 and 2006.

Is it safe to travel where cases of XDR TB have been reported?

Although MDR and XDR TB are occurring globally, they are still rare. HIV-infected travelers are at greatest risk if they come in contact with a person with MDR or XDR TB.

All travelers should avoid high risk settings where there are no infection control measures in place. Documented places where transmission has occurred include crowded hospitals, prisons, homeless shelters, and other settings where susceptible persons come in contact with persons with TB disease.

Air travel itself carries a relatively low risk of infection with TB of any kind.

What can health care providers do to prevent XDR TB?

Health care providers can help prevent MDR and XDR TB by quickly diagnosing cases, following recommended treatment guidelines, monitoring patients’ response to treatment, and making sure therapy is completed.

Providers should also ensure proper implementation of infection control procedures to prevent exposure to TB in hospitals or health-care settings where TB patients are likely to be seen.

Are immigrants putting the U.S. at increased risk for TB?

Persons applying to enter the U.S. with immigrant or refugee visas must complete a questionnaire about any symptoms of TB they may have and obtain a chest radiograph. If positive, the person submits sputum specimens for examination for TB bacteria. Persons identified as having infectious TB are not granted entry to the United States, until they have been treated.

Why haven’t we heard about XDR TB before now?

For some years we have seen isolated cases of very highly resistant TB around the world that we would today call XDR TB. The drugs used to treat TB have been around a long time and drug resistance has taken many years to develop. Over time, countries have improved their laboratory capacity to test for drug resistance and their ability to track the number of cases. All of these factors have contributed to an increase in reporting of cases of drug-resistant TB. With more cases being identified, the problem was more closely examined, defined, and given a name.

What is CDC doing to prevent XDR TB from becoming a bigger problem?

CDC is collaborating with other federal agencies and international partners to raise awareness and enhance strategies for TB prevention worldwide by

• Strengthening TB services for people living with HIV/AIDS
• Assembling outbreak response teams
• Improving access to TB drugs
• Developing international TB testing standards
• Building capacity of health care providers to diagnose and treat TB
• Reconvening the Federal TB Task Force
• Providing technical assistance to expand TB program capacity
• Supporting TB communication and education efforts

Additional Information

CDC. Questions and Answers About TB (2005)

CDC. Tuberculosis: General Information

CDC. Multidrug Resistant Tuberculosis

CDC. Tuberculosis Information for International Travelers

CDC. Extensively Drug-Resistant Tuberculosis - United States, 1993--2006

CDC. CDC’s Role in Preventing XDR TB