Reported Tuberculosis in the United States, 2021
Technical Notes
National Tuberculosis Surveillance System
Reporting areas (i.e., the 50 U.S. states, the District of Columbia [D.C.], New York City, Puerto Rico, and other U.S. jurisdictions in the Pacific Ocean and Caribbean Sea) provide information about tuberculosis (TB) cases to the Centers for Disease Control and Prevention’s (CDC’s) National TB Surveillance System (NTSS) by using a standard case report format, the Report of Verified Case of TB (RVCT). TB cases are verified according to the TB case definition for public health surveillance (Appendix A). TB cases are reported and counted according to the recommendations for reporting and counting TB cases (Appendix B).
TB Case Definition
The current TB surveillance case definition was adopted by the Council of State and Territorial Epidemiologists in 2009. TB cases are verified according to the following specified laboratory and clinical criteria (Appendix A).
Laboratory Criteria for Diagnosis
A TB case may be verified by the laboratory case definition with ≥1 of the following criteria: (1) isolation of Mycobacterium tuberculosis complex from a clinical specimen; or (2) demonstration of M. tuberculosis complex from a clinical specimen by nucleic acid amplification (NAA) test, or (3) demonstration of acid-fast bacilli (AFB) in a clinical specimen when a culture has not been or cannot be obtained or is falsely negative or contaminated.
Clinical Case Criteria
A TB case may be verified by the clinical case definition in the presence of all of the following clinical criteria: (1) a positive tuberculin skin test (TST) result or positive interferon-gamma release assay (IGRA) result for M. tuberculosis complex; and (2) other signs and symptoms compatible with TB (e.g., abnormal chest radiograph, abnormal chest computerized tomography [CT] scan, or other chest imaging study or clinical evidence of current disease); and (3) treatment with ≥2 anti-TB drugs; and (4) a completed diagnostic evaluation.
Provider Diagnosis
Provider diagnosis is not a component of the case definition for TB as described in Appendix A. However, when cases of TB are diagnosed but do not meet either the clinical or laboratory case definition, reporting areas have the option of verifying TB cases on the basis of provider diagnosis as described in Appendix B. Through 2008, the RVCT did not collect information about IGRA results. If an IGRA was performed in lieu of a TST, the RVCT would have indicated that a TST was not performed. Thus, culture- and smear-negative cases without a TST that were diagnosed by a positive IGRA result before 2008 were considered to have been confirmed by provider diagnosis. Starting in 2009, positive results for an IGRA have been included as part of the clinical case definition for TB confirmation. Anergic patients with a clinical presentation consistent with TB but without laboratory evidence of M. tuberculosis complex would also be an example of provider diagnosis and one that has not changed over time.
TB Case Verification Criteria Calculation
The software for TB surveillance developed by CDC includes a calculated variable for TB case verification called “VERCRIT.” In 2009, NAA test result, IGRA for M. tuberculosis complex at diagnosis, and initial chest CT scan or other chest imaging study were added to the VERCRIT calculation.
VERCRIT is calculated by using the following criteria in hierarchical order (beginning with the most preferred method of verification):
- positive culture,
- positive NAA test,
- positive AFB,
- clinical case confirmation, or
- provider diagnosis.
Reporting and Counting of TB Cases
TB cases that are verified but not countable for morbidity statistics should still be reported to CDC as a measure of programmatic and case management burden. However, data for noncountable TB cases are not included in this report.
Immigrants, refugees, and foreign visitors examined after arriving in the United States and receiving a diagnosis of TB disease requiring TB treatment should be reported and counted by the locality of their residence at the time the diagnostic evaluation for TB began. Persons residing in the United States ≥90 consecutive days (inclusive of report date) who are medically evaluated or treated for TB while in the United States should be reported and counted by the locality where the diagnostic evaluation for TB began.
RVCT Versions
In 2020, CDC published updates to the RVCT. This updated version, known as the “2020 RVCT,” includes items that are either new or revised from the previous RVCT that was published in 2009, known as the “2009 RVCT.” Since that time, reporting areas are gradually implementing the updates, and data for cases counted in 2021 were reported using either the 2009 RVCT or the 2020 RVCT.
The instructions for completing the 2020 RVCT are available in the 2020 RVCT instruction manual.14
Tabulation and Presentation of TB Data
This report presents summary data for TB cases counted by reporting areas through the end of 2021. TB cases are tabulated by year in which a reporting area verified a TB case and included it in its official annual TB case count. Since 2004, the published report has reflected updated information about the numbers of confirmed TB cases for each year from 1993 onward. U.S. totals include data from the 50 U.S. states and D.C.
Trend data are presented in Tables 1–26 and 29. Age-group tabulations are based on a person’s age during the month and year he/she was reported to the health department as having a presumptive TB case. State or metropolitan area tabulations are based on a person’s reported residence. Percentages and rates are calculated using nonrounded numbers.
Origin of Birth
CDC uses U.S. Census Bureau definitions for national origin, where persons are U.S.-born if they were entitled to U.S. citizenship at birth, i.e., they were born in the United States, certain U.S. territories (Puerto Rico, U.S. Virgin Islands, Guam, and Commonwealth of the Northern Mariana Islands) or elsewhere to at least one U.S. citizen parent (with certain minor exceptions). All other persons are categorized as non-U.S.–born.15
Rates
Rates are expressed as the number of cases reported each calendar year per 100,000 persons. Population denominators used in calculating TB rates were based on official census and midyear postcensal estimates from the U.S. Census Bureau. In Table 1 and Table 34, the U.S. total populations for 1990–1999 were taken from the Bridged-Race Intercensal Population Estimates for July 1, 1990–July 1, 1999: Single-year of age State estimates;16 populations for 2000–2009 were taken from the U.S. Census Intercensal Estimates of the Resident Population for the United States, Regions, States, and Puerto Rico for April 1, 2000–July 1, 2010;17 populations for 2010–2019 were taken from the U.S. Census Annual Estimates of the Resident Population for the United States, Regions, States, and Puerto Rico: April 1, 2010 to July 1, 2020;18 and populations for 2020 and 2021 were taken from the U.S. Census Annual Estimates of the Resident Population for the United States, Regions, States, and Puerto Rico for April 1, 2020 to July 1, 2021.19
During 2003, two modifications were made to the RVCT form: (1) multiple race entries (≥2 races reported for a person) were allowed, and (2) the previous category of “Asian or Pacific Islander” was divided into “Asian” and “Native Hawaiian or Other Pacific Islander.” To calculate rates for Table 2 and Table 5, denominators for 1993–1999 were obtained from the U.S. Census Monthly Postcensal Resident Population, by single year of age, sex, race, and Hispanic origin.20 For 2000–2009, denominators for Table 2 were obtained from U.S. Census Intercensal Estimates of the Resident Population by Sex, Race, and Hispanic Origin for the United States: April 1, 2000–July 1, 2010,21 and denominators for Table 5 were obtained from Intercensal Estimates of the Resident Population by Single Year of Age and Sex for States and the United States: April 1, 2000–July 1, 2010.21 For 2010–2019, denominators for Table 2 were obtained from the U.S. Census Monthly National Population Estimates by Age, Sex, Race, Hispanic Origin, and Population Universe for the United States: April 1, 2010 to December 1, 2020,22 and denominators for Table 5 were obtained from U.S. Census Annual Estimates of the Resident Population by Single Year of Age and Sex for the United States: April 1, 2010 to July 1, 2020.22 For 2020 and 2021, denominators for Table 2 were obtained from the U.S. Census Annual Estimate of the Resident Population by Sex, Race, and Hispanic Origin for the United States: April 1, 2020 to July 1, 2022,23 and denominators for Table 5 were obtained from the U.S. Census Annual Estimates of the Resident Population by Single Year of Age and Sex for the United States: April 1, 2020 to July 1, 2021.23 Four new trend tables with case rates were originally created for the 2020 Annual TB Report using data from 1994 and onward. Tables 3 and 4 report the trends of race-ethnicity among U.S.-born persons (Table 3) and non-U.S.–born persons (Table 4). Tables 6 and 7 report trends for different age groups among U.S.-born persons (Table 6) and non-U.S.–born persons (Table 7). Denominators for these new tables were obtained from the U.S. Census Bureau’s MDAT tool.24 Percentages by birth decade were calculated for U.S.-born persons (Table 8) and non-U.S.–born persons (Table 9) using cases from each birth decade cohort (derived from birth year of patient) divided by overall number of cases for each year.
The population source for nativity is the Current Population Survey,25 which is used to calculate case rates for U.S.-born and non-U.S.–born persons with diagnosed TB. U.S.-born populations include persons born in the 50 states and DC, those born abroad to U.S. parents, and those born in U.S. certain territories. To compute rates for Table 10, the population denominators for U.S.-born and non-U.S.–born persons for 1993 were obtained from Quarterly Estimates of the United States Foreign-Born and Native Resident Populations: April 1, 1990–July 1, 1999,26 and for 1994–2021 were obtained from U.S. Census Bureau’s MDAT tool.24 Denominators for computing 2021 rates in Table 27 were obtained from the U.S. Census Bureau’s MDAT tool.24
Rates by Country of Birth
To calculate U.S. TB rates by country of birth for Table 12, the average annual number of cases by country of birth reported to NTSS during 2017–2021 were used in the numerator. U.S. population estimates by country of birth were used for the denominator and were obtained from the U.S. Census Bureau, American Community Survey (ACS) Public Use Microdata Sample data, 2016–2020, 5-year file.27 At the time of this report, the 2017–2021 data had not been published. In the ACS, country of birth is self-reported, and persons born outside the U.S. are asked to report country of birth based on current international boundaries. Countries with population estimates of ≥10,000 persons are coded as a country; however, countries with population estimates of <10,000 persons are combined into regions (2016-2020 ACS 5-year PUMS Code Lists: Place of Birth [2017 or later]).2
Mortality Data
The annual mortality rate is calculated as the number of deaths caused by TB in that year, divided by the estimated population for the year, multiplied by 100,000 (Table 1). The number of deaths was obtained from CDC’s National Center for Health Statistics, Multiple Cause of Death Files, 1999–2020,28 available from CDC’s WONDER online database. Finalized 2021 TB-related death data were unavailable at the time of publication.
Initial Reason Evaluated for TB
Table 40 reflects the 2020 RVCT variable, Initial Reason Evaluated for TB, which modifies the Primary Reason Evaluated for TB Disease in the 2009 RVCT. In 2021, TB cases were submitted in either the 2009 or 2020 RVCT versions. The 2009 RVCT responses Targeted Testing, Health Care Worker, Employment/Administrative Testing, and Immigration Medical Exam were combined into the 2020 RVCT Screening response. Initial reasons for evaluation related to an Incidental Lab Result or Abnormal Chest Radiograph were combined into the Other category.
Extensively Drug-resistant (XDR) and Pre-XDR TB
In 2021, CDC adopted new definitions of extensively drug-resistant (XDR) and pre-XDR TB. Pre-XDR TB is caused by an organism that is resistant to isoniazid, rifampin, and a fluoroquinolone OR by an organism that is resistant to isoniazid, rifampin, and a second-line injectable (amikacin, capreomycin, and kanamycin). XDR TB is caused by an organism that is resistant to isoniazid, rifampin, a fluoroquinolone, and a second-line injectable (amikacin, capreomycin, and kanamycin) OR by an organism that is resistant to isoniazid, rifampin, a fluoroquinolone, and bedaquiline or linezolid.8
Completion of TB Therapy
Table 18, Table 49, and Table 50 present information on the completion of TB therapy (COT). Date and reason therapy was stopped (e.g., the patient completed therapy, or the patient died) are collected in the RVCT with a 2-year lag and were used to calculate COT percentages. Cases were stratified by the indicated length of therapy, based on American Thoracic Society, CDC, and Infectious Diseases Society of America treatment guidelines in effect during the period covered and the patient’s initial drug-susceptibility test results, age, and disease site.7
In Table 49, the first column lists the total number of cases reported during 2019. The remaining columns are grouped under 2 headings: therapy lasting ≤1 year indicated and therapy lasting >1 year indicated. To be counted in the data presented here, patients eligible to complete therapy in ≤1 year were alive at time of diagnosis and had to have initiated therapy with ≥1 drug. Eligible patients did not have rifampin resistance; did not die in ≤1 year after initiating therapy; did not move out of the country in ≤1 year after initiating therapy; and did not have meningeal TB, bone or joint TB, or TB of the central nervous system, regardless of age. Additionally, TB patients aged 0–14 years were ineligible to complete therapy in ≤1 year if they had disseminated disease (defined for this report as miliary TB, a positive TB blood culture, or a positive NAA test on a blood specimen). Patients with culture-negative disease, those with an unknown culture status, and those with culture-positive disease but unknown initial drug-susceptibility test results were included under the category of therapy of ≤1 year indicated.
For the group with an indicated length of therapy of ≤1 year, percentages are displayed for both COT in ≤1 year and for COT regardless of duration (i.e., duration of therapy ≤1 year or >1 year). For COT ≤1 year, the numerator included only those patients completing therapy in ≤366 days (based on the dates therapy was started and stopped). Patients with missing dates were classified as “treatment not completed” for this calculation.
COT percentages, regardless of duration, were calculated by dividing the number of patients reported as having completed therapy by the number of total eligible patients. Patients with an outcome other than completed therapy (i.e., moved, lost to follow-up, refused treatment, or other) were classified as “treatment not completed.” Patients with an unknown outcome were also classified as “treatment not completed.” For the group of indicated therapy length >1 year, only COT percentages regardless of duration are presented. Table 10 provides percentages for COT ≤1 year and for COT regardless of duration for the group with an indicated therapy of ≤1 year only.
TB Disease Site
Miliary disease should be reported as a pulmonary form of TB (Table 14 and Table 38). Beginning in 2009, miliary disease could not be classified as a TB disease site because it is a clinical or a radiologic finding and should be recorded under Initial Chest Radiograph, Initial Chest CT Scan, or Other Chest Imaging Study. During 1997–2008, miliary disease was classified as both an extrapulmonary and a pulmonary form of TB. In publications before 1997, miliary disease was classified as extrapulmonary TB, unless pulmonary disease was reported as the major disease site.
Reason Therapy Was Stopped
Beginning in 2009, Table 20 includes a patient’s adverse reaction to anti-TB drug therapy as an option for the reason therapy was stopped. The 2009 RVCT revision removed the option of “Moved” as a valid response to the variable Reason Therapy Stopped, and this option is therefore not reported after 2009. Those cases entered as “Moved” as reason therapy was stopped after 2009 are now categorized as Unknown.
Metropolitan Statistical Areas
Table 51 presents data by metropolitan statistical areas (MSAs). MSAs are defined by the White House Office of Management and Budget (OMB), and the definitions are based on the application of the 2020 OMB standards for delineating MSAs to U.S. Census Bureau population estimates.29 Table 51 includes MSAs with an estimated 2021 population of ≥500,000 persons.
The MSA definitions apply to all areas except the six New England states; those states are referred to collectively as the New England County Metropolitan Areas (NECMAs). MSAs are named for a central city in the MSA or NECMA, can include multiple cities and counties, and can cross state boundaries. For example, the TB cases and case rates presented for DC in Table 34 include only persons residing within DC’s geographic boundaries. However, the TB cases and case rates for the Washington, DC-MSA (Table 51) include persons residing within the multiple counties in the metropolitan area, including counties in Maryland, Virginia, and West Virginia. Cities or MSAs with incomplete or unavailable data were not included in the tables, and certain cities’ or MSAs’ total numbers might be underreported because of missing information.
National Tuberculosis Molecular Surveillance Center
The National Tuberculosis Molecular Surveillance Center (NTMSC), formerly known as the National Tuberculosis Genotyping Service, conducted the genotyping method mycobacterial interspersed repetitive units–variable number of tandem repeats (MIRU–VNTR) and has been performing whole-genome sequencing (WGS) since 2018. MIRU-VNTR along with spacer oligonucleotide typing (spoligotyping) conducted by CDC were used to assign M. tuberculosis isolates a genotype. As of June 30, 2022, NTMSC and CDC have discontinued genotyping using MIRU-VNTR and spoligotyping. However, NTMSC will continue prospective whole genome sequencing (WGS), to provide users with whole-genome multi-locus sequence typing (wgMLST) results. All isolates are prepared for long-term storage by the service.
Genotype Clustering
A genotype cluster comprises ≥2 cases in a jurisdiction during a specified period that have M. tuberculosis complex isolates with matching genotypes. The jurisdiction and period can vary on the basis of the specific application. Cases that are part of the same genotype cluster are likely to be related by TB transmission in some way; however, the cases might not be directly related (i.e., one person did not necessarily transmit M. tuberculosis to another person in the cluster) or recently related (i.e., both persons might have contracted TB from the same person, but the exposure might have happened years ago). In TB GIMS, a cluster is defined as ≥2 cases with matching genotypes (spoligotype and 24-locus MIRU-VNTR) in a single county within a 3-year period.
Mycobacterium bovis
For culture-confirmed TB cases that have been genotyped, Mycobacterium bovis can be defined primarily on the basis of spoligotyping results. The genotype-based definition for M. bovis requires either (1) the absence of spoligotyping spacers 3, 9, 16, and 39–43; the presence of ≥1 of the spacers 29–32; and the presence of ≥1 of the spacers 33–36; (2) the absence of spacers 3, 9, 16, and 39–43 and ≥2 copies of the repeated sequence at MIRU-VNTR locus 24 (i.e., loci 2687);30 or (3) determination based on microbiologic expertise. Data reported for 2004–2021 in Table 26 exclude cases of bacillus Calmette-Guérin M. bovis, which were defined as spoligotype 676773777777600 with x, y, or z in the second MIRU-VNTR position.
Recent Transmission
Estimates of recent transmission are based on a plausible source-case method that is described in detail elsewhere.9 Briefly, a given case is designated as attributed to recent transmission if a plausible source case with the following five characteristics can be identified in the national surveillance data: the same M. tuberculosis genotype, an infectious form of TB disease, patient’s residential location ≤10 miles of the given case, patient’s age ≥10 years, and a plausible source case ≤2 years before the given case. These criteria were field-validated using local epidemiologic assessments of whether 1,188 cases in three states were likely caused by recent transmission that was attributed to source cases reported during 1996–2000. Any given case with a plausible source case identified is included regardless of cluster size.
A TB case is designated as attributed to extensive recent transmission when the five criteria specified for recent transmission are met. Furthermore, the case belongs to a plausible transmission chain of at least six cases (i.e., the plausible source case and at least four other cases identified ≤3 years before the case being assessed, for a total of at least six cases).
These methods for estimating recent transmission can only be applied to culture-confirmed, genotyped cases that are eligible to be evaluated for recent transmission. Pediatric and other clinically diagnosed cases are likely underrepresented because cases without genotyping results are excluded. This limitation is especially relevant for TB cases in young children, which are most likely to be caused by recent transmission.
The percentages of cases attributed to recent transmission typically are higher in areas with fewer M. tuberculosis genotypes and where prevalent or common genotypes have been predominant for years; among relatively closed populations and remote areas (e.g., parts of Alaska) recent transmission might be overestimated. As evidenced by whole genome sequencing, genomic diversity might be greater than what is apparent using current genotyping methods among cases reported by areas bordering Mexico. Consequently, definitively distinguishing cases attributed to recent transmission from cases caused by reactivation of longstanding, untreated latent TB infection can be difficult using the methods reported here.
- Centers for Disease Control and Prevention. Division of Tuberculosis Elimination Strategic Plan 2016-2020. Accessed July 30, 2020. https://www.cdc.gov/tb/about/strategicplan.htm
- U.S. Census Bureau. Public Use Microdata Sample (PUMS) documentation. Accessed November 14, 2019. https://www.census.gov/programs-surveys/acs/microdata/documentation.2019.html
- Centers for Disease Control and Prevention. Reported Tuberculosis in the United States, 2019. Accessed August 3, 2021. https://www.cdc.gov/tb/statistics/reports/2019/default.htm
- Talwar A, Li R, Langer AJ. Association between Birth Region and Time to Tuberculosis Diagnosis among Non-US-Born Persons in the United States. Emerg Infect Dis. 2021;27(6):1645-1653. doi:10.3201/eid2706.203663
- Centers for Disease Control and Prevention. Reported Tuberculosis in the United States, 2020. Accessed August 26, 2022. https://www.cdc.gov/tb/statistics/reports/2020/default.htm
- Schwartz NG, Hernandez-Romieu AC, Annambhotla P, et al. Nationwide tuberculosis outbreak in the USA linked to a bone graft product: an outbreak report. Lancet Infect Dis. Published online August 4, 2022:S1473-3099(22)00425-X. doi:10.1016/S1473-3099(22)00425-X
- Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis. 2016;63(7):e147-e195. doi:10.1093/cid/ciw376
- Langer AJ, Starks AM. Surveillance definitions for extensively drug resistant (XDR) and pre-XDR tuberculosis. Accessed August 31, 2022. https://www.cdc.gov/tb/publications/letters/2022/surv-def-xdr.html
- France AM, Grant J, Kammerer JS, Navin TR. A field-validated approach using surveillance and genotyping data to estimate tuberculosis attributable to recent transmission in the United States. Am J Epidemiol. 2015;182(9):799-807. doi:10.1093/aje/kwv121
- Mindra G, Wortham JM, Haddad MB, Powell KM. Tuberculosis Outbreaks in the United States, 2009-2015. Public Health Rep. 2017;132(2):157-163. doi:10.1177/0033354916688270
- Raz KM, Talarico S, Althomsons SP, et al. Molecular surveillance for large outbreaks of tuberculosis in the United States, 2014–2018. Tuberculosis. 2022;136:102232. doi:10.1016/j.tube.2022.102232
- Li R. Notes from the Field: Tuberculosis Outbreak Linked to a Contaminated Bone Graft Product Used in Spinal Surgery — Delaware, March–June 2021. MMWR Morb Mortal Wkly Rep. 2021;70. doi:10.15585/mmwr.mm7036a4.
- World Health Organization. Global Tuberculosis Report, 2021. Accessed August 30, 2022. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2021
- Centers for Disease Control and Prevention. 2020 Report of Verified Case of Tuberculosis (RVCT) Instruction Manual, Appendix B: Recommendations for Reporting and Counting Tuberculosis Cases. Accessed September 12, 2022. https://www.cdc.gov/tb/programs/rvct/InstructionManual.pdf
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- Scott C, Cavanaugh JS, Pratt R, Silk BJ, LoBue P, Moonan PK. Human Tuberculosis Caused by Mycobacterium bovis in the United States, 2006-2013. Clin Infect Dis. 2016;63(5):594-601. doi:10.1093/cid/ciw371