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										For the latest information, please visit Uniting for Ukraine: Information for TB ProgramsReturn to Main Menu
Uniting for Ukraine – Drug Resistance Background and Recommendations
August 1, 2022
Dear Colleagues,
**Overview and Summary**
This letter is in follow up to the letter of June 21, 2022 about tuberculosis (TB) screening in the Uniting for Ukraine program. In the Uniting for Ukraine program, Ukrainian parolees are required to undergo testing with a TB-specific interferon-gamma release assay (IGRA) and subsequent TB diagnostic studies as needed. Parolees are also required to be vaccinated for several other infections. On July 14, the U.S. Department of Homeland Security  extended the time period for completing the TB requirement  from 14 days to 90 days.
The Division of Tuberculosis Elimination (DTBE), Centers for Disease Control and Prevention (CDC), has received questions about preventive treatment regimens for Ukrainian parolees who are diagnosed with latent TB infection following post-arrival testing because of reports of prevalent drug-resistant TB in Ukraine. The data from CDC and the World Health Organization (WHO) indicate a prevalence rate of multidrug-resistant (MDR) TB among Ukrainians who had culture-confirmed TB in the United States or in Ukraine of 13% to 32.6%. These rates underlie concerns that have been raised that drug resistance could be common among persons coming from Ukraine who have latent TB infection.
Latent TB infection in Ukrainian parolees should be treated in accordance with current guidelines from the National Tuberculosis Controllers Association (NTCA) and CDC, unless drug susceptibility test results for the presumed source case support a conclusion of drug-resistant latent TB infection. If drug-resistant latent TB infection is suspected, clinical consultation should be obtained for assistance in selecting drugs in an empirical latent TB infection treatment regimen. TB disease must be excluded before any regimen for treating latent TB infection is started. When Ukrainian parolees are being examined for possible TB disease, microbiological testing should include rapid molecular methods for detecting drug resistance.
**Drug Resistance Data from the World Health Organization**
In the World Health Organization (WHO) 2020 TB profile for Ukraine, 17,533 new and relapse cases were reported.  Of those, 4,257 cases were MDR TB or at least rifampin resistant and 1,172 were extensively drug resistant (XDR) or pre-XDR TB. WHO projected that TB was approximately 50% underreported in Ukraine, and testing and reporting for drug resistance in Ukraine are not systematic (Int J Tuberc Lung Dis 2018 ;22:197-205). Of culture-confirmed cases, 32.6% were MDR TB, including XDR and pre-XDR TB (WHO TB High Burden Countries, ECDC WHO Information Note).
**Drug Resistance Data from the Centers for Disease Control and Prevention**
For 2014–2020 in CDC’s National TB Surveillance System, 122 cases of TB were reported in non–U.S.-born persons with Ukraine as the place of birth. Of these cases, 104 (85%) were culture confirmed, and 102 had susceptibility results for at least isoniazid and rifampin. Any isoniazid resistance was reported for 24 (24%), any rifampin resistance for 13 (13%), and MDR TB for 13 (13%), which included XDR or pre-XDR TB for 3 (3%). The pre-2021 definitions for XDR and pre-XDR TB were used.
From U.S. immigration panel sites in Ukraine during 2016–2021, the results of medical examinations for 54,493 Ukrainians who were applying for immigrant or refugee admission to the United States were reported to CDC’s Division of Global Migration and Quarantine: 36 applicants had Class A Active TB, for a prevalence rate of 66/100,000 persons examined. Of the 36 cases, 31 (86%) were culture confirmed: 6 (19%) were drug resistant besides MDR or XDR TB, and 7 (23%) were MDR TB, which included 2 (6%) XDR TB. Two of the five cases that were not culture confirmed were diagnosed with rapid molecular tests that indicated rifampin resistance.
The TB epidemiology of the Uniting for Ukraine parolees might be dissimilar to that of the Ukraine-born persons already in the United States or to that of the applicants at the immigration panel sites in Ukraine. Still, the data from WHO and CDC indicate that drug resistance could be common among the parolees who have latent TB infection or TB disease.
**Treatment of Latent Tuberculosis Infection when Background Drug Resistance is Prevalent**
The influence of prevalent drug resistance on the effectiveness of preventive therapy for a national population has not been determined. In a U.S. observational study during an outbreak of isoniazid- and streptomycin-resistant TB, the infected contacts who were treated with only isoniazid were more likely to have TB disease during follow up than persons who were treated with rifampin-based regimens, and the breakthrough cases were isoniazid resistant (Am J Respir Crit Care Med 1996;154:1473-1477). In an overseas observational study during an MDR TB outbreak, fluoroquinolone-based regimens that were selected from the drug susceptibility for the source cases appear to have prevented TB disease in infected contacts (HHS Public Access doi:10.5588/ijtld.13.0028).
**Treatment Regimen Recommendations**
CDC has not published latent TB infection treatment guidance that is specific to a country of origin or to a background prevalence of drug resistance. The recommended regimens that have been studied in randomized clinical trials should be prescribed for Ukrainian parolees who have latent TB infection, unless the drug-susceptibility results for the presumed source case are known and indicate that drug-resistant latent TB infection is likely. The selection of drugs for empirical regimens that have not been studied in randomized clinical trials should be guided by the susceptibility results of a presumed source case. For Ukrainian parolees who have latent TB infection and who describe being exposed to drug-resistant TB when drug susceptibility test results are unavailable, consultation from a TB control official or a clinician at a regional TB Center of Excellence is advisable.
TB disease must be excluded with chest radiography and other studies as guided by clinical findings before any regimen for treating latent TB infection is started. When Ukrainian parolees are being examined for possible TB disease, microbiological testing should include rapid molecular methods for early detection of drug resistance.

Sincerely,
Terence Chorba, MD, DSc, LLM, MPH, MPA, FACP, FIDSAChief, Field Services Branch, Division of Tuberculosis EliminationNational Center for HIV, Viral Hepatitis, STD, and TB PreventionCenters for Disease Control and Prevention
Adam J. Langer, DVM, MPH, DACVPM
Chief, Surveillance, Epidemiology, and Outbreak Investigations Branch, Division of Tuberculosis Elimination
National Center for HIV, Viral Hepatitis, STD, and TB Prevention
Centers for Disease Control and Prevention
							
					
						Page last reviewed:  August 2, 2022					Content source: 	Division of Tuberculosis Elimination, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention homeTuberculosisBasic TB Factsplus iconHow TB SpreadsLatent TB Infection and TB DiseaseSigns & SymptomsTB Risk FactorsExposure to TBTB PreventionVaccinesTB & HIV CoinfectionTB and DiabetesTB TermsPersonal StoriesTesting & Diagnosisplus iconWho Should be TestedTesting for TB InfectionTesting in BCG-Vaccinated PersonsTB Screening and Testing of Health Care PersonnelTesting During PregnancyDiagnosing latent TB infection and TB diseaseTreatmentplus iconDeciding When to Treat Latent TB InfectionTreatment Regimens for Latent TB Infection (LTBI)Treatment for TB DiseaseAdverse EventsTB Treatment of Persons Living with HIVTB Treatment and PregnancyTB Treatment for ChildrenFrequently Asked QuestionsDrug-Resistant TBResearchplus iconTB Epidemiologic Studies Consortiumplus iconResearch ProjectsPublicationsTB Trials Consortiumplus iconStudy DescriptionsBackgroundBehavioral & Social Science ResearchHealth Care Settingsplus iconTB Infection Control in Health Care SettingsResources for TB Screening and Testing of Health Care Personnelplus iconFrequently Asked QuestionsTB in Specific Populationsplus iconHealth DisparitiesAsian PersonsBlack or African American PersonsHispanic or Latino PersonsChildrenPregnancyCorrectional FacilitiesPeople Experiencing HomelessnessInternational TravelersLaboratory Informationplus iconDrug Susceptibility TestingFalse-Positive Investigation ToolkitInterim Laboratory Biosafety Guidance for XDR  tuberculosis strainsModel Performance Evaluation Program (MPEP)Rapid Molecular Testing to Detect Drug-Resistant TB in the USplus iconExecutive SummaryIntroductionBackground on Tests for Molecular Detection of DRGeneral Considerations and Principles for a Molecular DR Testing ServicePossible Scenarios and Scope of Testing for a Molecular DR Testing ServiceResearch NeedsGeneral Recommendations of the Expert PanelCommunication Plan for the ReportRecommendationsReferencesPanel Members and CDC ParticipantsAppendix 1Appendix 2Appendix 3The Uses of Nucleic Acid Amplification Tests for the Diagnosis of TBplus iconGeneral ConsiderationsGeneral Recommendations of the Expert PanelRecommendations to ACET, CDC, DTBEData & Statisticsplus iconTB Incidence in the United StatesReported TB in the US, 2022 Surveillance Reportplus iconNational DataReporting Area DataRisk FactorsDemographicsTB Treatment and Case OutcomesDrug-Resistant TBMolecular SurveillanceTuberculosis in the United States, 2022 (Slide Set)Archived Surveillance Reports and Slide Sets2021 State and City ReportArchived State and City ReportsProfessional Resources & Toolsplus iconTools for Healthcare ProvidersResources for TB Programsplus iconStrengthening Civil Surgeons’ Capacity to Improve LTBI Surveillance and Outcomes Among Status AdjustersNotice of Funding Opportunity (NOFO)Program EvaluationTB Centers of ExcellenceTB Elimination AllianceTB Genotypingplus iconConventional TB GenotypingWhole Genome SequencingTB GIMSAnalytic ToolsLatent Tuberculosis Infection ResourcesPublications & Productsplus iconPatient and Public MaterialsFact SheetsGuidelinesplus iconControl & EliminationDrug-Resistant TBInfection Control & PreventionLaboratory & GenotypingTB & HIVTB in Specific PopulationsTesting & DiagnosisTreatmentVaccines & ImmunizationsArchived TB GuidelinesGuides & Toolkitsplus iconAggregate ReportsCDC TB Surveillance TrainingCore CurriculumEffective TB Interviewing for Contact InvestigationEthnographic GuidesFalse-Positive Investigation ToolkitForging Partnerships to Eliminate TuberculosisGuide to Application of GenotypingLTBI: A Guide for Primary Health Care ProvidersMantoux Tuberculin Skin Testing ProductsReport of Verified Case of Tuberculosis (RVCT)Self-Study ModulesTB Contact Investigation Interviewing Skills CourseTB eDOT ToolkitUnderstanding the TB Cohort Review ProcessNewslettersplus iconTB Notes, No. 4, 2023TB Notes, No. 3, 2023TB Notes. No. 2, 2023TB Notes. No. 1, 2023TB Notes, No. 4, 2022TB Notes, No. 3, 2022TB Notes, No. 2, 2022TB Notes, No. 1, 2022TB Notes, No. 4, 2021TB Notes, No. 3, 2021TB Notes, No. 2, 2021TB Notes, No. 1, 2021Pamphlets, Brochures, Bookletsplus iconQuestions and AnswersPatient Education SeriesTuberculosis - Get the FactsTuberculosis - The Connection between TB and HIV12-Dose Regimen for Latent TB Infection-Patient Education BrochurePostersplus iconMantoux Tuberculin Skin Test Wall ChartWorld TB DayThink TBStop TBTake on TBReports & Articlesplus iconDTBE Authored Journal ArticlesTuberculosis Laboratory Aggregate ReportsSlide Setsplus iconIntroduction to TuberculosisEpidemiology of Tuberculosis Among Non-U.S.​–Born Persons in the United States, 1993–2016Self-Study Modules on Tuberculosis, 1-5 Slide SetsThe Tuberculosis (TB) in Correctional Settingsplus iconFacilitator GuideIntroduction to TB GenotypingEpidemiology of Tuberculosis in Correctional Facilities, United States, 1993-2017Prevention and Control of Tuberculosis in Correctional and Detention FacilitiesGuidelines for Preventing the Transmission of M. TB in Health care SettingsInvestigation of Contacts of Persons with Infectious TBEpidemiology of Pediatric Tuberculosis in the United StatesTargeted Tuberculosis Testing and Treatment of Latent Tuberculosis InfectionElectronic Tools & ResourcesWeb-Based Courses & Webinarsplus iconTB 101 for Health Care WorkersContent SyndicationInfographicsplus iconSocial Media GraphicsCustomizable Take on TB Infographic with InstructionsEventsWorld TB Dayplus iconU.S. TB ChampionsHistoryFeaturesplus iconTB Risk FactorsTreating Latent TB Infection with Short-Course RegimensWorld Tuberculosis (TB) Day 2021World Tuberculosis (TB) Day 2020Linksplus iconState TB Control OfficesAbout Usplus iconMission Statement and Activitiesplus iconDTBE Strategic PlanNational TB Program ObjectivesOrganization ChartAdvisory Groupsplus iconFederal TB Task Force To receive email updates about this page, enter your email address: Email Address			What's this?				Submit


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