TB trends and TB genotyping

Management of a TB Contact Investigation for Public Health Workers Albuquerque, NM October 1, 214 TB trends and TB genotyping Marcos Burgos MD October 1, 214 Marcos Burgos, MD has the following disclosures to make: No conflict of interests No relevant financial relationships with any commercial companies pertaining to this educational activity TB trends and TB genotyping Management of a TB Contact Investigation for Public Health Workers October 1, 214 Marcos Burgos MD. Medical Director of the Tuberculosis Program of New Mexico Department of Health Associate Professor University of New Mexico School of Medicine 1

Objectives Describe demographics characteristics and trends of TB cases Discuss the basic process and goals of TB GIMS Discuss studies with the use of Molecular epidemiology 2

TB pathogenesis 9% no sequellae Primary infection (tuberculin positive) 5% primary TB (within 2 years) 5% reactivation (later in life) TB pathogenesis M. tuberculosis Virulent vs. attenuated bacilli Susceptible vs. resistant host Active TB 8 million new cases per year 1% 9% TB infection 2 billion people 3

Reported TB Cases United States, 1982 212* No. of Cases *Updated as of June 1, 213. Year Cases per 1, TB Case Rates by Race/Ethnicity,* United States, 23 212** 35. 3. 25. 2. 15. 1. 5.. 23 24 25 26 27 28 29 21 211 212 Hispanic or Latino American Indian or Alaska Native Asian Black or African American Native Hawaiian or Other Pacific Islander White *All races are non-hispanic. **Updated as of June 1, 213. TB Case Rates by Age Group and Race/Ethnicity,* United States, 212 6 5 Hispanic or Latino Cases per 1, 4 3 2 1 Under 5 5 14 15 24 24 44 45 64 65 American Indian or Alaska Native Asian Black or African American Native Hawaiian or Other Pacific Islander *All races are non-hispanic. Persons reporting two or more races accounted for less than 1% of all cases. 4

Reported TB Cases by Race/Ethnicity,* United States, 212 Black or African American (22%) Hispanic or Latino (29%) American Indian or Alaska Native (1%) Asian (31%) Native Hawaiian or Other Pacific Islander (1%) White (16%) *All races are non-hispanic. Persons reporting two or more races accounted for less than 1% of all cases. 2, Number of TB Cases in U.S.-born vs. Foreign-born Persons, United States, 1993 212* No. of Cases 15, 1, 5, 1993 1994 1995 1996 1997 1998 1999 2 21 22 23 24 25 26 27 28 29 21 211 212 U.S. born Foreign born *Updated as of June 1, 213 Trends in TB Cases in Foreign-born Persons, United States, 1992 212* No. of Cases Percentage 1, 9, 8, 7, 6, 5, 4, 3, 2, 1, 7 6 5 4 3 2 1 Number of Cases Percentage of Total Cases *Updated as of June 1, 213 5

TB Case Rates in U.S.-born vs. Foreign-born Persons, United States, 1993 212* Cases per 1, 4. 35. 3. 25. 2. 15. 1. 5.. U.S. Overall U.S. born Foreign born *Updated as of June 1, 213. Countries of Birth of Foreign-born Persons Reported with TB, United States, 212 Other Countries 39% Mexico (21%) Philippines (12%) Haiti (3%) Guatemala (3%) China (6%) Vietnam (7%) India (8%) Percent of Foreign-born with TB by years of Residence in U.S. Prior to Diagnosis, 212 1 8 6 4 2 Mexico Philippines India All Other Foreignborn Unknown* <1 year 1-4 years 5 years *Foreign-born TB patients for whom information on length of residence in the U.S. prior to diagnosis is unknown or missing 6

1 Primary Anti-TB Drug Resistance, United States, 1993 212* % Resistant 5 Isoniazid MDR TB *Updated as of June 1, 213. Note: Based on initial isolates from persons with no prior history of TB. Multidrug resistant TB (MDR TB) is defined as resistance to at least isoniazid and rifampin 3 Primary MDR TB in U.S.-born vs. Foreign-born Persons United States, 1993 212* % Resistant 2 1 U.S. born Foreign born *Updated as of June 1, 213. Note: Based on initial isolates from persons with no prior history of TB. MDR TB defined as resistance to at least isoniazid and rifampin. Estimated HIV Coinfection in Persons Reported with TB, United States, 1993 212* 7 6 % Coinfection 5 4 3 2 1 Aged 25 44 All Ages *Updated as of June 1, 213 Note: Minimum estimates based on reported HIV-positive status among all TB cases in the age group 7

TB Cases by Residence in Correctional Facilities, Age 15, United States, 1993-212* 12 1 8 6 4 2 6.% 5.% 4.% 3.% 2.% 1.%.% No. of Cases Percent of Total Cases *Updated as of June 1, 213 Note: Resident of correctional facility at time of TB diagnosis TB Cases Reported as Homeless in the 12 Months Prior to Diagnosis, Age 15, United States, 1993-212* 16 14 12 1 8 6 4 2 8.% 7.% 6.% 5.% 4.% 3.% 2.% 1.%.% No. of Cases Percent of Total Cases *Updated as of June 1, 213 Note: Homeless within past 12 months of TB diagnosis 8

Molecular Epidemiology Conventional Epidemiology Molecular Markers Disease Control, Pathogen virulence & evolution A Central Tenet Distinct pattern = Epidemiologically unlinked Shared pattern = common source 9

Outbreak of TB In 26, eight TB cases and a ninth incarceration-related case were identified In 1996, the source patient had pulmonary TB but completed only two weeks of treatment. The source patient lived in four different locations while contagious. The outbreak cases had matching isolate spoligotypes The source patient's isolates showed a mixed mycobacterial population with both MIRU patterns. Traditional and molecular epidemiologic methods linked eight secondary TB cases to a single source patient Public Health Rep. 29 Jul-Aug Urban Epidemiology of Tuberculosis Question? What proportion of tuberculosis is due to recent transmission? Methods: Genotype all isolates of MTB that caused disease in a given urban area Unique genotypes = reactivation of latent infection Identical genotypes = recent transmission Of 473 patients studied, 191 had TB as a result of recent transmission. Small et al., NEJM 1994;33:173 1

Outbreak Investigation TB and HIV Exquisite susceptibility Rapid progression Daley et al., NEJM 1992; 326:231-5 re-infection How common it is? 18 patients retreated for TB 44% re-infection Re-infection an important mechanism of recurrence? Caminero JL, AJCCRM, 21; 717 11

General Perceptions of immigrants & TB 1) Immigrants have high rates of infection and have a stronger predisposition to become active cases 2) Immigrants transmit tuberculosis to the general population TB in Mexican Immigrants in San Francisco 9 (21%) were infected in SF 34 (79%) reactivated their infection Only one case resulted in transmission to a US born individual Jasmer et al. Int J TB Lung Dis 536-541, 1997 12

TB in Immigrants in San Francisco 1. Transmission from immigrants to US born individuals is limited 3. Transmission occurs more from US cases to immigrants TB Genotyping Information Management System (TB GIMS) Stores and manages genotyping data on TB patients in the United States Allows users to submit and track Mycobacterium tuberculosis isolates to and from the contract genotyping labs Provides immediate notification of genotyping results and updates to TB labs and programs 13

TB Genotyping Information Management System (TB GIMS) Links isolate data to patient-level surveillance data Provides reports on genotype clusters, including national genotype distribution Provides national, state, and county maps of genotype clusters Objectives of TB GIMS To improve access to and dissemination of genotyping information nationwide To serve as a standard database that local programs can use to Track MTB complex isolates Receive and update genotyping information To provide a way to alert users about potential TB outbreaks in their jurisdictions Definition for Tuberculosis Genotyping in the United States Spoligotype: 3771 Initial 12-locus MIRU- VNTR 1 : 223325173533 Sequentially assigned for each unique spoligotype and initial 12-locus MIRU- VNTR combination PCRType: PCR2 + Additional 12-locus MIRU-VNTR (MIRU2): 444534423428 2 Sequentially assigned for each unique spoligotype and 24-locus MIRU-VNTR combination GENType: G1 1 Mycobacterial interspersed repetitive unit variable number tandem repeat 2 The complete set of 24 loci is referred to as 24-locus MIRU-VNTR and is used for GENType designation for genotype in the U.S. 14

National Tuberculosis Genotyping Surveillance Coverage * by Year, United States, 24 212 Proportion of culture confirmed TB cases genotyped (%) 1% 9% 8% 7% 6% 5% 4% 3% 2% 1% % 91.3% 93.5% 93.5% 86.8% 8.9% 81.6% 68.5% 7.1% 52.6% 24 25 26 27 28 29 21 211 212 National Indicator 94% * The proportion of positive cultures with at least one genotyped isolate Number and Percent of Unique* and County-GENType Clustered ** Cases, United States, 21 212 17,669 (79%) 4,585 (21)% Unique Clustered * Unique case is a case with a spoligotype and 24-locus locus MIRU-VNTR (GENType) that does not match any other case in that county during the specified 3-year time period ** Two or more cases with matching spoligotype and 24-locus locus MIRU-VNTR (GENType) within a county during the specified 3-year time period Number of Cases in a Cluster Number of County-based Tuberculosis Genotype Clusters * by Cluster Size, United States, 21 212 1 9 8 7 6 5 4 3 2 996 257 25 1 3 9 2-case cluster 3-case cluster 4-9 case cluster 1-19 case >=2 case cluster cluster * Genotype cluster is defined as two or more cases with matching spoligotype and 24-locus MIRU-VNTR (GENType) within a county during the specified 3- year time period 15

Tuberculosis Genotype Clusters by TB GIMS * Alert Levels **, United States, 21-212 High Alert, 112 (7%) Medium Alert, 361 (23%) No Alert, 1,69 (69%) * Tuberculosis Genotyping Information Management System ** Alert level is determined by the log likelihood ratio statistic (LLR) for a given cluster, identifying higher than expected geospatial concentrations for a TB genotype cluster in a specific county, compared to the national distribution of that genotype; TB GIMS generates alert level notifications based on this statistic: No alert is indicated if LLR is between 5, medium is for LLR of 5.1 1 and high alert is for clusters with LLR >1 Tools for epidemiology of M. tuberculosis 16