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Extensively Drug-Resistant Tuberculosis (XDR TB)>

Extensively Drug-Resistant Tuberculosis (XDRTB) – Update

October 20, 2006Dear Colleagues:Several of us from CDC attended the first meeting of the GlobalXDR TB Task Force meeting, convened by the World HealthOrganization (WHO) in Geneva, Switzerland, October 9-10,2006. This meeting was convened to develop a rapid responseto the emerging problem of extensively drug-resistanttuberculosis (XDR TB).*Please recall the original publication on XDR TB in the March 24,2006

Morbidity and Mortality Weekly Report

entitled “Emergence of Mycobacterium tuberculosis with ExtensiveResistance to Second-Line Drugs -- Worldwide, 2000 – 2004 ” (PDF). This report provided an alert that XDR TB has emergedworldwide as a threat to public health and TB control, raisingconcerns of a future epidemic of virtually untreatable TB, anddocumented the known occurrence of XDR TB globally, as wellas here in the United States—with U.S. patients with XDR TBbeing 64% more likely to die during treatment than patientswith multidrug-resistant (MDR) TB. We also reported that newanti-TB drug regimens, better diagnostic tests, andinternational standards for second line drug-susceptibilitytesting are urgently needed for effective detection andtreatment of MDR and XDR TB.CDC is collaborating with national and international healthagencies to provide leadership, technical support, and capacitybuilding to ensure proper action is taken to limit thedevelopment and spread of XDR TB. CDC also participated in anexpert consultation held in Johannesburg, South Africa,September 7-8, 2006, organized by the South African MedicalResearch Council (MRC) and WHO. This consultation wasconvened because of concerns raised by recent reports fromKwaZulu-Natal (KZN) province in South Africa, describing arecent outbreak of XDR TB in an HIV-infected population,characterized by alarmingly high mortality rates. Of 544patients found with culture-positive TB, 221 had MDR TB. Of these 221 MDR TB cases, 53 were described by localinvestigators as XDR TB. Of these 53 patients, 44 were testedfor HIV and all were positive; 52 of 53 patients died, onaverage within 25 days -- including those benefiting fromantiretroviral drugs. Investigators from the University of KZNhave also documented the existence of this same XDR TB strainin 28 healthcare institutions throughout KZN province.Additionally, we learned of anecdotal reports from medicalauthorities who care for gold miners describing patientsexperiencing unexplained high death rates from TB inneighboring parts of South Africa. These different data fromSouth Africa likely represent the “tip of the iceberg” of highlydrug-resistant TB predominantly affecting HIV-infectedindividuals, and likely present in other regions of the world.XDR TB poses a grave public health threat, especially inpopulations with high rates of HIV and where there are fewhealth care resources. Recommendations outlined by the WHOGlobal Task Force on XDR TB include:

Preventing XDR TB through strengthening TB and HIVcontrol

Management of XDR TB suspects in high and low HIVprevalence settings:

Accelerate access to rapid tests for rifampicin resistance,to improve case detection of all patients suspected of multidrug-resistant TB (MDR TB) so that they can be

.diagnosis is potentially life saving to those who are HIVpositive.Program management of XDR TB and treatment design inHIV negative and positive people:

Adhere to WHO Guidelines for the ProgrammaticManagement of Drug Resistant TB;

Improve MDR TB management conditions;

Enable access to all MDR TB second-line drugs,under proper conditions;

Ensure all patients with HIV are adequately treatedfor TB and started on appropriate antiretroviraltherapy.

Laboratory XDR TB definition:

XDR TB is defined as resistance to at least rifampicin andisoniazid from among the first line anti-TB drugs (which isthe definition of MDR TB) in addition to resistance to anyfluoroquinolone, and to at least one of three injectablesecond-line anti-TB drugs used in TB treatment(capreomycin, kanamycin, and amikacin).

Infection control and protection of health careworkers with emphasis on high HIV prevalencesettings.

Immediate XDR TB surveillance activities and needs:

Strengthen laboratory capacity to diagnose, manage andsurvey drug resistance; Commence rapid surveys of drug-resistant TB so that the extent and size of the XDR TBepidemic, and its association with HIV, can bedetermined.

Advocacy, communication and social mobilization:

Initiate information-sharing strategies that promoteeffective prevention, treatment, control of XDR TBat global and national levels and also in high HIVprevalence settings;

Strengthen communication with affectedcommunities and individuals;

Develop a fully-budgeted plan with the resourcesand funding required to address XDR TB, includingthrough necessary improvements in overall TBcontrol and HIV care in the immediate and mediumterm;

Initiate resource mobilization.Many of the lessons-learned from the MDR TB outbreaks in theUnited States in the 1990s are being brought to bear toaddress this urgent situation. This includes expertise in rapidoutbreak response, surveillance, building laboratory capacity,and infection control, all while keeping a focus on overall TBprogram strengthening as the crucial element to prevent thedevelopment and transmission of MDR and XDR TB. Our countryhas accrued more than 10 years of experience addressing drug-resistance in resource-limited settings and contributedsubstantively to development of the DOTS-Plus strategy andglobal policy on MDR TB. This puts us in an unparalleled positionto respond to the current crisis; we will rely on nationalpartners such as the National TB Controllers Association andthe National Coalition for the Elimination of Tuberculosis,American Thoracic Society, Infectious Diseases Society of America, and Staff from the Division of Tuberculosis Elimination(DTBE) and the Global AIDS Program (GAP) to continue andexpand work with colleagues in WHO, U.S. Agency forInternational Development, South Africa MRC, and with otherinternational partners to provide technical assistance, shareexpertise, and mobilize financial and technical resources torespond to action items to address XDR TB.In addition to providing our expertise and technical assistanceto our international partners, we must also ensure that ourdomestic programs are capable of diagnosing, treating, andpreventing TB, including XDR TB. The hard work by many instate and local health department programs has resulted in adecline in TB trends, including in 2005 the lowest reportednumber of persons diagnosed with TB disease in the UnitedStates. However, that very success makes us vulnerable to thecomplacency and neglect that come with fewer personssuffering with TB. In the 1970s and early 1980s, the nation letits guard down and TB control efforts were neglected. Thecountry became complacent about TB, and many states andcities redirected TB prevention and control funds to otherprograms. Consequently, the trend toward elimination was

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reverse an e na on exper ence an unprece en eresurgence of TB, with a 20% increase in TB cases reportedbetween 1985 and 1992. Many of these were in persons withdifficult-to-treat MDR TB, and in persons coinfected with HIV.Listed below are some very important areas of focus and needfor U.S. TB programs to prevent the emergence of additionalXDR TB and to eliminate TB in the United States.Maintaining Control: By strengthening current TBcontrol, treatment, and prevention systems, weensure the ability to diagnose and provide propertreatment to people with active TB disease and,thus, prevent spread to others; this will alsoprevent the emergence of MDR TB and XDR TB.Accelerating the Decline: By finding better methodsof identifying and treating latent TB infection andimproving strategies for reaching at-riskpopulations, we will speed our progress towardelimination.Developing New Tools for Diagnosis, Treatment, andPrevention: Through research to develop moreeffective methods of testing for latent TB infection,better drugs to treat latent TB infection and activeTB disease, and an effective TB vaccine, we willfind vital ways to stop the transmission of TB.Engaging in Global TB Prevention and Control: Inproviding leadership, contributing technical support,and forming international partnerships, we improveglobal health. Worldwide control of TB is in thenation’s best interest.Mobilizing Support for TB Elimination: By reachingleaders of high-risk groups, we can work togetherto eliminate a disease that burdens theircommunities.Monitoring Progress: By assessing the impact of ourelimination efforts, we can continually monitor ourprogress and identify and address any lapses in ourefforts.This recently described problem of XDR TB constitutes anurgent global health reality, instead of an urgent health threat-- and is deserving of commensurate attention and action.Furthermore, the experience and expertise gained in ourcountry from having to respond in the early 1990s to the HIV-associated resurgent TB and MDR TB will hopefully shed lightand provide relevant lessons. We may need to call upon you toprovide the necessary response, and will keep you informed of progress and new developments as these occur.Sincerely yours,Kenneth G. Castro, M.D.Assistant Surgeon GeneralDirector, Division of Tuberculosis EliminationNational Center for HIV, STD and TB PreventionCoordinating Center for Infectious Disease* Extensively drug resistant tuberculosis (XDR TB) wasoriginally defined as the presence of Mycobacteriumtuberculosis isolates resistant to at least isoniazid and rifampin(MDR TB), plus additional resistance to at least three of the sixclasses of second-line drugs used to treat persons with MDRTB. These forms of tuberculosis are both more difficult andexpensive to treat. XDR TB is of particular concern amongpersons with HIV infection or other conditions that weaken thehost’s immunity. These persons are more likely to develop TBdisease once they become infected with Mycobacteriumtuberculosis, and have been associated with a higher risk of death. The greatest concern is that XDR TB leaves somepatients virtually untreatable with currently available drugs.