Multidrug-Resistant Tuberculosis in Hmong Refugees Resettling from Thailand into the United States, 2004--2005

In December 2003, the U.S. Department of State initiated a resettlement program for 15,707 Hmong refugees who had been displaced from Laos and were living on the grounds of Wat Tham Krabok, a Buddhist temple in Thailand. In January 2005, reports of tuberculosis (TB) cases among refugees still in Thailand and refugees who had arrived in the United States, including some cases caused by multidrug-resistant* (MDR) strains, prompted a 1-month travel suspension. After enhanced screening in Thailand and intensified TB-control measures in the United States, resettlement resumed on February 16. A majority of the Hmong refugees in Thailand and the United States with TB diagnosed were started on treatment and monitored. As of July 15, no additional TB cases had been diagnosed among newly resettled Hmong refugees. U.S. health departments should continue to ensure careful monitoring for TB among this refugee group.

Approximately 50,000--70,000 refugees resettle in the United States each year (1). Before resettlement, all refugees undergo medical screening to prevent importation of diseases that pose an immediate public health risk. The standard TB-screening algorithm, used in early 2004 to evaluate Hmong refugees in Thailand, includes a medical history and physical examination for all applicants and a chest radiograph for persons aged >15 years. Applicants with clinical or radiologic findings suggestive of TB disease submit three sputum specimens for acid-fast bacilli (AFB) smear microscopy. Those with positive results must begin anti-TB treatment and have follow-up specimens with consistently smear-negative results before travel to the United States is allowed.^† The standard premigration algorithm was revised in May 2004 to add requirements for mycobacterial culture and drug-susceptibility testing.

During June 2004--January 2005, the United States resettled 9,459 Hmong refugees in 20 states (Table and Figure). As the newly arrived refugees underwent health assessments at local health departments and in private health-care facilities, 37 TB cases, including four MDR cases, were reported. This finding coincided with assessments in Thailand, where 17 (33%) of 52 culture-confirmed cases among refugees were determined to be MDR. In contrast, among all new TB cases reported in the United States during 2004 with drug-susceptibility results, 1% were MDR TB (2). Hmong refugee travel to the United States was suspended to allow for epidemiologic investigation and to prevent further importation of TB cases.

In January 2005, coordinated investigations were conducted in Thailand and the United States by the International Organization for Migration, CDC, the Thailand Ministry of Public Health, the U.S. Department of State, the U.S. Department of Health and Human Services Office of Global Health Affairs, and state and local health departments to describe the epidemiology of TB disease and to direct TB-control measures among the refugees. The case definition for TB disease required either 1) bacteriologic evidence (i.e., sputum-smear microscopy or culture) or 2) a decision to initiate TB treatment in the context of radiographic abnormalities or clinical features consistent with TB.

Thailand

The investigation in Thailand began with an evaluation of laboratory procedures, which excluded the possibility of false-positive culture results. Medical records of patients being treated for TB disease were reviewed, and all known patients were interviewed. Patient living quarters were mapped with global positioning system (GPS) technology to assess for potential geographic clustering of cases. Classmates of refugee children and other non-Hmong contacts were screened by chest radiograph and, if indicated, by sputum-smear microscopy.

During March 2004--January 2005, a total of 272 refugees, including 11 (4%) children aged <15 years, received a diagnosis of TB disease. Thirty (11%) of the 261 persons aged >15 years had AFB sputum-smear--positive pulmonary TB. One person tested positive for human immunodeficiency virus (HIV), 258 tested negative, and results for two persons were unknown. Children aged <15 years were not routinely tested for HIV. Medical records and interviews revealed that three (18%) of the 17 culture-confirmed MDR TB patients had been treated previously for TB disease. Nine (53%) reported at least weekly contact with another MDR TB patient, and seven were linked through a social network that centered around a patient with sputum-smear--positive MDR TB. GPS mapping revealed widespread distribution of TB cases throughout the Hmong living quarters in Wat Tham Krabok (an area of 0.5 km²). No additional smear-positive TB cases were detected during screenings of classmates and other non-Hmong contacts in Thailand (n = 327).

In February 2005, the premigration screening algorithm for Hmong refugees was revised again. All refugees aged >6 months were rescreened with chest radiographs, and those aged 6 months to 10 years also underwent tuberculin skin testing. In addition, laboratory capacity was increased with addition of automated culture methods, access to MDR TB medications was ensured, and a team of physicians and nurses was established to provide expert case management for TB patients. Since the implementation of this enhanced algorithm, an additional 73 cases of TB disease have been diagnosed, including seven cases of MDR TB, resulting in an overall total of 345 TB cases (including 24 MDR). Patients are permitted to travel to the United States only after they have completed anti-TB treatment. As of July 15, a total of 341 Hmong refugees in Thailand had undergone treatment for TB disease under directly observed therapy, and 197 (58%) had completed treatment.

United States

Health departments in areas affected by the resettlement intensified surveillance for TB among the newly arrived refugees and continued providing diagnostic and treatment services for patients and their contacts. In addition, public health officials, resettlement agencies, and Hmong community organizations collaborated to determine educational needs and resources for sharing TB information with refugees and other members of the Hmong community in both Thailand and the United States.

California, where approximately one third of the refugees were resettled, reported 24 (65%) of the 37 TB cases, including 10 among children aged <15 years who, as directed by the initial screening algorithm, had not received a premigration TB screening. The 14 patients aged >15 years tested negative for HIV infection. Of the eight culture-confirmed cases in California, one (13%) had rifampin mono-resistance, and four (50%) were resistant to isoniazid, rifampin, ethambutol, and streptomycin. All four MDR TB patients had AFB sputum-smear--positive results. One MDR TB patient, who had initially tested rifampin-susceptible, acquired resistance to rifampin during treatment in Thailand. Local health departments have identified no secondary cases beyond immediate household members, although contact investigations continue.

Since resettlement resumed on February 16, approximately 3,500 additional Hmong refugees have been resettled to 22 states; none had TB diagnosed after arrival. Health departments continue to ensure that all recently arrived refugees are screened and treated for TB disease and infection when necessary. Health-care providers are asked to report to local and state health departments any additional TB cases detected in Hmong refugees who have arrived since June 2004.

Reported by: International Organization for Migration, Geneva, Switzerland. Thailand Ministry of Public Health--US CDC Collaboration; Dept of Disease Control, Thailand Ministry of Public Health. Fresno County Dept of Community Health. Sacramento County Dept of Health and Human Svcs. California Dept of Health Svcs. Michigan Dept of Community Health. Minnesota Dept of Health. Ohio Dept of Health. Wisconsin Dept of Health and Family Svcs. Bur of Population, Refugees, and Migration, US Dept of State. Office of Global Health Affairs, US Dept of Health and Human Svcs. Div of Global Migration and Quarantine, National Center for Infectious Diseases; Div of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, CDC.

Editorial Note:

The global incidence of TB disease is increasing (3), and an increasing percentage of TB cases in the United States are occurring among foreign-born persons (2). The Institute of Medicine has recommended that the United States strengthen its role in global TB-control activities, including enhancement of overseas TB screening and treatment capacity (4). The standard of care for TB case management includes high-quality diagnostic services and medications, consistent use of directly observed therapy, and standardized monitoring of outcomes. Emergence of MDR TB can be prevented by adhering to this standard.

The World Health Organization estimates that, when standard laboratory services are available and diagnostic criteria are applied, at least 65% of passively detected pulmonary TB cases among adults will have AFB smear-positive results (5). In this investigation, only 11% of the cases diagnosed among refugees aged >15 years awaiting resettlement were smear positive, suggesting that active surveillance might have led to overdiagnosis. Culture confirmation of 24 MDR cases in Thailand and four MDR cases in the United States in the same refugee population within 16 months is cause for concern. Why the reported number of TB cases among resettled refugees was higher in California and why MDR TB cases among resettled refugees were found only in California remains unknown.

Because of the high prevalence of TB disease among the refugees described in this report, all are at risk for recent exposure to Mycobacterium tuberculosis. Recent infection is a major risk factor for progression to TB disease (6), but latent TB infection (LTBI) is not routinely treated in Thailand. Therefore, to prevent M. tuberculosis transmission and progression to TB disease in the United States, the domestic refugee health and TB programs affected by this resettlement should ensure postmigration monitoring and services for refugees, including treatment of LTBI.

These investigations and responses have required and will continue to demand considerable public health resources. Per person, the estimated costs of detecting disease and treating patients with LTBI range from $208 to $11,125, and the direct medical costs associated with TB and MDR TB disease range from $3,800 to $137,000, depending on case complexity.^§ These projections underestimate the costs for treating Hmong refugees because they exclude the additional expenses of providing culturally appropriate outreach, interpretation, and transportation services.

The annual number of immigrants to the United States continues to increase (1), and TB is the medical condition most frequently diagnosed among applicants for permanent residence (CDC, unpublished data, 2005). The number of imported TB cases described in this report would have been substantially greater if overseas screening had not been enhanced. For Hmong refugees resettling from Thailand, mycobacterial cultures and drug-susceptibility testing helped ensure appropriate treatment of patients with TB disease. These and other enhancements to standard premigration screening guidelines are under consideration for future U.S.-bound refugees and immigrants from other countries with a high TB burden.

References

1. US Department of Homeland Security. 2003 yearbook of immigration statistics. Washington, DC: US Government Printing Office; 2004. Available at http://uscis.gov/graphics/shared/statistics/yearbook/2003/2003yearbook.pdf.
2. CDC. Trends in tuberculosis---United States, 2004. MMWR 2005;54:245--9.
3. Dye C, Watt CJ, Bleed DM, Hosseini SM, Raviglione MC. Evolution of tuberculosis control and prospects for reducing tuberculosis incidence, prevalence, and deaths globally. JAMA 2005;293:2767--75.
4. Institute of Medicine. Ending neglect: the elimination of tuberculosis in the United States. Washington, DC: National Academies Press; 2000.
5. World Health Organization. Treatment of tuberculosis: guidelines for national programs. Geneva, Switzerland: World Health Organization; 2003.
6. CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR 2000;49(No. RR-6).
7. Lambert L, Rajbhandary S, Quails N, et al. Costs of implementing and maintaining a tuberculin skin test program in hospitals and health departments. Infect Control Hosp Epidemiol 2003;24:814--20.
8. Marks SM. Potential cost savings by TB treatment regimen choice. TB Notes 2003;4:25--8. Available at http://www.cdc.gov/nchstp/tb/notes/tbn_4_03/upd_clinical.htm.
9. Taylor Z, Marks SM, Rios Burrows NM, Weis SE, Stricof RL, Miller B. Causes and costs of hospitalization of tuberculosis patients in the United States. Int J Tuberc Lung Dis 2000;4:931--9.
10. Rajbhandary SS, Marks SM, Bock NN. Costs of patients hospitalized for multidrug-resistant tuberculosis. Int J Tuberc Lung Dis 2004;8:1012--6.

* Defined as resistant to at least isoniazid and rifampin.

^† Medical Examination of Aliens, 42 C.F.R. § 42; 2004.

^§ Estimated costs are derived from several studies (7--10). Direct medical costs of TB screening and treatment of LTBI caused by presumed isoniazid-susceptible strains are approximately $208--$311 per person without DOT. For each infected contact of a patient with MDR TB, California estimates follow-up and treatment costs to be $11,125 (T. Porco, California Department of Health Services TB Control Program, personal communication, 2005). If drug-susceptible TB disease is diagnosed, treatment costs are approximately $3,800 under daily DOT. Costs increase an additional $19,000 when patients require hospitalization, as do approximately 50%. Direct medical costs associated with MDR TB hospitalization average $53,000 and range from $15,000 to $137,000 per case. For each study, costs were updated to 2004 U.S. dollars by taking the costs determined by that study and multiplying them by the ratio of the medical-care component of the consumer price index for 2004, divided by the index for the year of the study, or, for costs dominated by personnel, a similar ratio of wages.

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Date last reviewed: 8/3/2005