US TB Outbreaks Highlight Investigative
and Therapeutic Challenges
By Matthew Watson, July 26, 2013
In its March 2013 report on tuberculosis (TB) trends for 2012, the US Centers for Disease Control and Prevention (CDC) reported 9,951 new cases of TB in the United States, a number that translates to an incidence rate of 3.2 cases/100,000.1 Of those cases, 6,243 (63%) occurred in foreign born individuals. Although 2012 marked the 20th year of declining TB incidence rates in the US, surveillance, control, and treatment continue to be challenging for public health professionals and healthcare providers, as evident in the experience with several recent outbreaks that have occurred already in 2013.
South Carolina Outbreak
On March 8, a physician in Greenwood County, South Carolina, reported a TB case to the SC Department of Health and Environmental Control. The patient in question was a maintenance worker at an elementary school. The public health investigation resulted in the screening of 1,364 individuals, 94 of whom tested positive for TB (including 53 students).2 Of these, 13 progressed to active TB and were placed on a standard TB treatment regimen. No cases of drug resistance were reported in relation to this outbreak.
MDR-TB Outbreak in Wisconsin
On April 11, a case of multidrug-resistant TB (MDR-TB; defined as a strain that is resistant to both isoniazid and rifampin) was diagnosed in a female member of an “immigrant community” in Sheboygan, WI.3 The patient’s family included children who were enrolled in the local high school and middle school. The Sheboygan County Department of Health and Human Services initiated an investigation, still ongoing, that screened approximately 130 individuals and has identified 9 cases of active TB, none of whom shared the patient’s drug resistance profile. To finance the necessary public health investigation and interventions, the Wisconsin State Legislature appropriated roughly $5 million.3
On June 18, 2013, officials at the Fairfax County Health Department announced the investigation of 3 cases of TB at a Virginia high school.4 The first case was diagnosed in December 2012, and 2 subsequent cases were diagnosed in June. In all, 430 families were found to be at increased risk of infection and were contacted by the health department for screening.
XDR-TB on US-Mexico Border
On March 1, 2013, the Wall Street Journal reported that a Nepalese man detained at the US-Mexico border was diagnosed with extensively drug-resistant TB. XDR-TB is defined as a strain that is resistant to isoniazid and rifampin, plus any fluoroquinolone, and at least one of 3 second-line drugs.5 The contact tracing investigation in this case was complicated because the man had traveled a circuitous route through multiple countries before being detained and diagnosed by US Immigrations and Customs Enforcement officials. No further information on this investigation is publicly available, but to date, the case has not resulted in any documented transmission.
The CDC has reported that TB incidence rates are 11.5 times higher in foreign-born residents than in people born in the US.1 This case illustrates the need for heightened awareness of and surveillance for TB among foreign born people, especially those visiting from countries where there are high rates of drug resistant disease.
Novel Therapeutic for MDR-TB Approved
There has been one recent addition to the TB treatment armamentarium: On December 28, 2012, the US Food and Drug Administration approved Sirturo (bedaquiline) for inclusion in an active MDR-TB treatment regimen.6 Bedaquiline acts by inhibiting mycobacterial ATP synthase. 7 Safety and effectiveness have been evaluated in 2 Phase 2 clinical trials, and the drug was approved under fast-track, priority review, and orphan-drug designations.
Additionally, on July 25, 2013, the FDA approved Cephied’s Xpert MTB/RIF assay, which detects the presence of MTB-complex DNA, and mutations associated with rifampin resistance.8
In April of this year, the CDC reported a shortage of a purified protein derivative (PPD), the tuberculin product used to screen for TB infection in contact investigations and for screening employees and patients in hospitals and healthcare facilities across the country.9 Addressing this shortage should be a priority.
Rapid identification and reporting of active TB cases contributes significantly to disease control. Identification of possible cases relies on astute clinical observation and timely reporting, but also depends on rapid diagnosis. Molecular diagnostic technologies, such as whole genome sequencing, can perform diagnosis and susceptibility testing within hours or days instead of the weeks required for culture-based methods.10 Increasing their availability and use in clinical and public health labs should be a priority, particularly given the advent of MDR- and XDR-TB. The percentage of new drug-resistant TB cases in the US may be small (1.6% of cases in 2011)1 but the cost of managing and treating those cases is significantly higher than managing nonresistant cases.
- US Centers for Disease Control and Prevention. Trends in tuberculosis—United States, 2012. MMWR. March 22, 2013. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6211a2.htm. Accessed July 18, 2013.
- DHEC update—TB investigation, Greenwood County [news release]. Columbia, SC: South Carolina Department of Health and Environmental Control; June 18, 2013. http://www.scdhec.gov/administration/news/2013/nr20130618-01.htm. Accessed July 18, 2013.
- Knox R. Tuberculosis outbreak shakes Wisconsin city. NPR. July 18, 2013. http://www.npr.org/blogs/health/2013/07/18/200871130/tuberculosis-outbreak-shakes-wisconsin-city. Accessed July 18, 2013.
- Rees Shapiro T. Fairfax Health Department investigates tuberculosis cases at Lee High School. Washington Post. June 20, 2013. http://articles.washingtonpost.com/2013-06-20/local/40087931_1_tuberculosis-cases-health-and-school-officials. Accessed July 18, 2013.
- McKay B. Dangerous TB patient detained on U.S. border. Wall Street Journal. March 1, 2013. http://online.wsj.com/article/SB10001424127887323978104578332461533970412.html. Accessed July 18, 2013.
- FDA approves first drug to treat multi-drug resistant tuberculosis [news release]. Silver Spring, MD: US Food and Drug Administration; December 31, 2012. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333695.htm. Accessed July 18, 2013.
- Bedaquiline [package insert]. Titusville, NJ: Janssen Therapeutics, Division of Janssen Products, LP. December 2012. http://www.who.int/tb/challenges/mdr/Package_insert_bedaquiline.pdf. Accessed July 25, 2013.
- Cepheid Receives FDA Market Authorization for Xpert MTB/RIF. PR Newswire. July 25, 2013. http://www.prnewswire.com/news-releases/cepheid-receives-fda-market-authorization-for-xpert-mtbrif-216996721.html. Accessed July 26, 2013.
- Nationwide shortage of tuberculin skin test antigens: CDC recommendations for patient care and public health practice. US Centers for Disease Control and Prevention, Emergency Preparedness and Response, Health Alert Network. April 12, 2013. http://emergency.cdc.gov/HAN/han00345.asp. Accessed July 18, 2013.
- Köser CU, Bryant JM, Becq J. Whole-genome sequencing for rapid susceptibility testing of M. tuberculosis. N Engl J Med. 2013 Jul 18;369(3):290-2.