Multidrug-Resistant Tuberculosis (MDR-TB)

Abstract & Commentary

By Lin H. Chen, MD

Assistant Clinical Professor, Harvard Medical School; Director, Travel Resource Center, Mount Auburn Hospital, Cambridge, MA

Dr. Chen reports no financial relationships relevant to this field of study.

Synopsis: The estimated number of global MDR-TB cases in 2004 was 4.3% of all TB cases, and Eastern Europe had the highest proportions of MDR-TB cases. The largest numbers of MDR-TB cases were from China, India, and the Russian Federation. Travelers with TB exposure in these countries or Eastern Europe should be assessed for the possible exposure to MDR-TB and treated accordingly.

Source: Zignol M, et al. Global incidence of multidrug-resistant tuberculosis. J Infect Dis. 2006;194:479-485.

The World Health Organization/International Union against Tuberculosis and Lung Disease Global Project on Anti-tuberculosis Drug Resistance began collecting its data in 1994 on drug resistance in 90 countries. Cases are defined as new cases when patients had received treatments for less than one month (or none at all), and previously treated cases when patients had received treatment for at least one month.

In 2004, the estimated worldwide MDR-TB cases numbered 424,203, which was 4.3% of all TB cases. About 181,408 MDR-TB cases were estimated to have occurred among previously treated TB cases, and 242,794 MDR-TB cases were estimated to have occurred among new cases. Thus, 2.7% of new cases and 18.5% of previously treated cases were MDR-TB. Eastern Europe, the Western Pacific region, Southeast Asia, and the Eastern Mediterranean region have the highest proportions of MDR-TB in new cases. Additionally, Eastern Europe, the Eastern Mediterranean region, and the Western Pacific region have the highest proportions of MDR-TB in previously treated cases.

The prevalence of MDR-TB was highest in Eastern Europe, affecting 9.9% of new cases and 39.9% of previously treated cases of TB. Southeast Asia and the Western Pacific region follow. China, India, and the Russian Federation contribute the largest numbers of MDR-TB cases, accounting for 62% of the total.

As expected, the proportion of patients who had prior TB treatment correlated with the proportion of newly diagnosed MDR-TB cases. However, the proportion of patients with TB and HIV co-infection was negatively correlated with the proportion of MDR-TB cases among previously treated cases. The authors attributed this finding to the high mortality in patients co-infected with TB and HIV, who likely died from the initial TB infection.

Based on the assumption that the duration of disease with MDR-TB is between 2 and 3 years (although the actual duration is not known), the authors further estimate that the global prevalence of MDR-TB ranges from 850,000–1,300,000 cases.

Commentary

Mycobacterium tuberculosis is an aerobic bacillus that grows slowly, but is highly contagious through airborne transmission. TB is one of the leading causes of morbidity and mortality worldwide, with an estimated incidence of 14.6 million infections and causing 1.7 million deaths in 2004.1 The largest number of new TB cases in 2004 occurred in the south-east Asia region, but the estimated per capita incidence is highest in sub-Saharan Africa, at nearly 400 cases per 100,000 population.1 In Eastern Europe, the per capita incidence increased during the 1990s, but has been declining since 2001. At the present, one-third of the world's population is infected with TB, and 5–10% of infected individuals become ill sometime in life.1

The worldwide problem of TB has been attributed to urban crowding, homelessness, and the HIV epidemic. Drug-resistance in TB appeared in the early 1990's, due to inadequate regimens, incomplete courses of treatment, and noncompliance with therapy. Even more worrisome is the emergence of extensively drug-resistant (XDR) TB. The CDC reported that during 2000-2004, 20% of worldwide TB isolates were MDR and 2% were XDR.2

In the United States, the 2005 TB rate was 4.8 cases per 100,000, the lowest since national reporting began in 1953.3 However, the TB rate in foreign-born individuals was 8.7 times that of US-born individuals.3 Hispanics, blacks, and Asians had much higher TB rates (7.3, 8.3, and 19.6, respectively) compared to caucasians.3 Furthermore, high proportions of TB cases in Hispanics, blacks, and Asians were in foreign-born persons (75%, 27%, and 96%, respectively). [CDC trends] The states of California, Florida, Georgia, Illinois, New Jersey, New York, and Texas had the highest numbers of TB cases, accounting for about 60% of the national total.3 The majority of foreign-born TB cases in 2005 were reported in persons from Mexico, the Philippines, Vietnam, India, and China.3

Within the United States, the MDR-TB rate was higher in foreign-born than US-born (1.6% vs 0.6%, respectively); Mexico, the Philippines, and Vietnam were the most common countries of origin for foreign-born individuals with MDR-TB.3 It is unclear whether the foreign-born individuals acquired MDR-TB cases in their countries of previous residence or after arrival in the United States.

Because travelers may have TB exposure in highly-endemic countries, the CDC recommend that travelers who anticipate prolonged stays or frequent travel to countries with high TB prevalence have a tuberculin skin test (PPD) before travel. Assuming the reaction is negative, they should have a repeat test approximately three months after travel.4 The two-step baseline test, which is recommended for persons with occupational exposure to TB, should also be advised for travelers who anticipate repeated prolonged travel or an extended stay.3 Additionally, annual screening with a PPD should also be considered in expatriates.

Crowded environments may increase the risk of exposure to TB during travel, and should be discussed with the traveler. Travelers who will be working in health-care settings where TB patients may be encountered should consult infection control or occupational health experts about personal respiratory protective devices (eg, N-95 respirators), along with appropriate fitting and training.

Another concern for travelers is the transmission of TB on commercial aircraft, which has been reported.5 The risk of TB transmission on an airplane was greater on long flights that were ≥8 hours; proximity of a passenger to an infectious person increases the risk of exposure to TB because of the possibility of inhaling small droplets containing M. tuberculosis.5 WHO issued recommendations to prevent the transmission of TB in aircraft and to guide potential investigations. Persons known to have infectious TB should not travel by commercial airlines, and should limit their travel.

References:

  1. WHO. Tuberculosis fact sheet. Available at www.who.int/mediacentre/factsheets/fs104/en. Accessed August 26, 2006.
  2. CDC. Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs-worldwide, 2000-2004. MMWR Morb Mortal Wkly Rep. 2006:55:301-305.
  3. CDC. Trends in tuberculosis — United States, 2005. MMWR Morb Mortal Wkly Rep. 2006;55:305-308.
  4. CDC. Health Information for International Travel 2005-2006. Atlanta: US Department of Health and Human Services, Public Health Service, 2005.
  5. Kenyon TA, et al. Transmission of multidrug-resistant Mycobacterium tuberculosis during a long airplane flight. N Engl J Med. 1996;334:933-938.