Pediatric Tuberculosis in Los Angeles County: An Update

Pediatric Tuberculosis in Los Angeles County: An Update Julie Higashi, MD PhD Director, Tuberculosis Control Program March 2, 2019 0 Pediatricians will be the driving force of TB elimination in California TB elimination = 1/1,000,000 cases 1 1

Natural History of TB Not everyone who is exposed to TB develops TB infection 90% Remain latently infected Exposure to infectious TB Latent TB infection (LTBI) 5% Progression to active TB disease Reactivation Of those infected, 5% develop primary active TB disease Most people complete treatment. About 10% are dead at diagnosis or die during treatment Los Angeles County in the Nation 2017 TUBERCULOSIS CASE COUNTS California*: 2056 cases New York State: 806 cases Los Angeles: 511 cases * California case count includes Los Angeles County cases Texas: 1127 cases Florida: 549 cases 3 2

TB Cases By County, CALIFORNIA 2017 San Diego (n=237) Santa Clara (n=186) Orange (n=186) Alameda (n=124) San Francisco (n=107) Los Angeles (n=511) 0 100 200 300 400 500 600 Number of TB cases Number of TB Cases and Rates: LA County 2000-2017 1200 Number of TB Cases Incidence Rate 16.0 Number of TB Cases 1000 800 600 400 200 0 1056 1040 1019 11.4 11.4 11.0 946 10.1 927 9.7 903 9.4 879 9.1 813 791 8.4 8.6 702 675 680 7.2 7.3 7.3 625 6.7 661 7.0 586 602 6.2 6.3 550 5.7 511 5.3 14.0 12.0 10.0 8.0 6.0 4.0 2.0 0.0 Incidence Rate per 100,000 Persons Year of Confirmation Data exclude Pasadena and Long Beach TB cases and are provisional to change. Based on TRIMS data, updated 2/26/18. Population estimates distributed by Los Angeles County, Internal Services Department. *2017 incidence rate was calculated using 2016 LAC population estimate. 5 3

TB in LA County: Overall Burden Annually 500-600 cases of active TB disease 1,800-3,000 suspected TB disease evaluations 3,000-5,000 contacts to infectious TB 1,000,000 LA County residents infected with TB 6 TB in Children 0-4 Years of Age: LA County 2003-2017 Number of Cases Ages 0-4 % of TB Cases 35 10% Number of TB Cases Ages 0-4 30 25 20 15 10 5 0 21 2.2% 31 27 26 27 24 2.9% 2.9% 3.5% 3.3% 3.0% 14 2.0% 15 2.2% 29 4.3% 9 1.4% 18 15 2.7% 2.6% 5 0.8% 8 9 1.4% 1.8% 9% 8% 7% 6% 5% 4% 3% 2% 1% 0% Percent of all TB Cases Year of Confirmation Data exclude Pasadena and Long Beach TB cases and are provisional to change. Based on TRIMS data, updated 2/26/18. 7 4

Pediatric TB cases 2012-2016 Pediatric TB = Age <15 10 25 cases per year 1.8% - 4% of all TB cases Young children = Age <5 8 18 cases per year 1.5% - 2.7% of all TB cases TB in young children = transmission in US! 8 Nativity of Pediatric TB Cases 2012-2016 Hispanic Asian Black NH White 0-4 44 9 1 1 5-14 19 4 1 2 Total 77.8% 16% 2.5% 3.7% Non-US-born 6% 31% 50% 0% US-born 94% 69% 50% 100% 89% are US-born vs adult TB 82% are non-us-born TB transmission from non-us-born family 9 5

Countries of Birth of TB cases in LAC 10 How do TB Cases Occur in California? 13% 7.5% Recent Importation Transmission 835 of 11,149 cases occurred within 1 year of arrival in U.S. (2010-2014) 79.5% Reactivation of remote infection Cases not from importation or recent transmission >2,000 Cases Per Year CDC plausible source case method* * France et al, Am J Epidemiol. 2015 11 6

Year of TB elimination in California Extrapolation based on current rate of decline* Rate per 1 Million 1000 100 10 1 Actual Current decline (-4%) 2040 Elimination (-14%) Elimination 2114 0 2040 1985 1995 2005 2015 2025 2035 2045 2055 Year 2065 2075 2085 2095 2105 2115 2125 * Average annual decline in case rate 2005-2014 12 What does elimination mean in California? Elimination by 2040 Averted Tuberculosis 2015(Current) 2040 (cumulative) Rate (case per million) 55 <1 - Cases 2133 39 25,000 Deaths 210 4 2,500 Direct costs (2015 dollars) $72 Million $1.3 Million >$850 million 2040 cases based on 2014 US Census Estimate of California Population: 38.8 million Elimination definition: WHO. Framework towards TB Elimination in Low-Incidence Countries. 2014 Deaths estimated as 10% of active cases 13 Direct costs estimated using average cost per case in 2015 ($33,692). Includes only direct medical costs for case. 7

Estimated TB Infection prevalence, awareness, treatment California, 2015 NHANES 2011-2012 applied to California population Millions of persons 2.5 2.0 1.5 1.0 1.8M U.S.-born Foreign-born 0.5 0.0 20% 12% LTBI prevalence Aware of LTBI Treated for LTBI 14 TB Infection Assessment Algorithm Risk Assessment and Symptom Review Evaluation complete No TB risk TB test Yes, TB risk Evaluate for active TB Yes, TB symptoms Negative Positive Chest x-ray Treatment not indicated Normal Candidate for Rx of latent TB http://ph.lacounty.gov/tb/providertoolkit.htm Abnormal Evaluate for active TB 8

TB Infection Assessment Algorithm Risk Assessment and Symptom Review Evaluation complete No TB risk TB test Yes, TB risk Evaluate for active TB Yes, TB symptoms Negative Positive Chest x-ray Treatment not indicated Normal Candidate for Rx of latent TB http://ph.lacounty.gov/tb/providertoolkit.htm Abnormal Evaluate for active TB http://publichealth.lacounty.gov/tb/ 17 9

http://ph.lacounty.gov/tb/providertoolkit.htm 18 http://ph.lacounty.gov/tb/providertoolkit.htm 19 10

TB Infection Assessment Algorithm Risk Assessment and Symptom Review Evaluation complete No TB risk TB test Yes, TB risk Evaluate for active TB Yes, TB symptoms Negative Positive Chest x-ray Normal Abnormal Treatment not indicated Candidate for Rx of latent TB http://ph.lacounty.gov/tb/providertoolkit.htm Evaluate for active TB Red Book 2018 Childhood TB Infection The recommended age for use of IGRAs for the diagnosis of TB has been decreased to 2-years-old. For preventive treatment of TB infection, there are now three options offered: 3HP = 12 weeks of once-weekly, high-dose INH + rifapentine [ 2-years-old and up] 4R = 4 months (120 doses) of once-daily Rifampin 9H = 9 months (270 doses) of once-daily INH Recommended rifampin dose is now 15mg/kg, regardless of indication. 21 11

Key points about IGRAs A negative IGRA does not rule out TB disease IGRA results are dependent upon specimen handling Even with good specimen handling, IGRA results can be variable - Serial testing in healthcare workers (considered low risk) 6-8% conversion with IGRA, 75% reverted upon repeat testing. Dorman et al., AJRCCM 2014. IGRA performance in pediatric population is reliable 3 year cohort of children < 15 followed, IGRA in BCG vaccinated children predicted nonprogression to TB disease without treatment after > 5 years of follow up (Grinsdale, et al., JPID, 2014 22 Red Book 2018 Childhood TB Infection The recommended age for use of IGRAs for the diagnosis of TB has been decreased to 2-years-old. For preventive treatment of TB infection, there are now three options offered: 3HP = 12 weeks of once-weekly, high-dose INH + rifapentine [ 2-years-old and up] 4R = 4 months (120 doses) of once-daily Rifampin 9H = 9 months (270 doses) of once-daily INH Recommended rifampin dose is now 15mg/kg, regardless of indication. 23 12

MMWR:Update of Recommendations for Use of Once Weekly INH-RFP Regimen to Treat LTBI Infection q Children Non-inferior to 9 months of INH 3HP now recommended for use in children ages 2-17 years old q q Self-administered therapy (SAT) Completion rates: SAT 78% vs. DOT 85% (non-inferior) 3HP can now be administered by SAT or DOT in people > 2 years old, depending upon local practice and the patient HIV Non-inferior to 9 months of INH 3HP may now be administered with select compatible ARV regimens Villarino E, et al., JAMA Pediatrics, Jan 2015 Belknap R, et al., Ann Intern Med. November, 2017 Sterling T, et al., AIDS, Jun, 2016 MMWR, June 29, 2018, 65(27);723-726 24 INH-RPT (3HP) q Advantages: Less hepatotoxicity (~ 7x less than INH) Greater adherence (82% INH-RPT vs. 69% INH) q Disadvantages: Multiple drug interactions Pill burden Flu-like syndrome (2.2%) 25 13

Summary Los Angeles County has a high burden of TB Most pediatric cases in LA County represent transmission in the county and are considered preventable cases Increases in treatment of pediatric TB infection by as little as 2-4 fold will accelerate TB elimination and bend the curve for LA County! IGRA performs well in the pediatric population at risk Rifamycin based regimens have higher completion rates than INH 26 Acknowledgements Alicia Chang, MD, MSc, Deputy Director and Ramon Guevara, PhD Supervising Epidemiologist Shom Dasgupta-Tsinikas, MD, FAACP, Physician Specialist Pennan Barry MD, MPH, TB Control Branch, California Department of Public Health 14

http://publichealth.lacounty.gov/tb/ Thank you! Join our Coalition! 28 jhigashi@ph.lacounty.gov Rx for Prevention http://rx.ph.lacounty.gov/ RxTB0517 - Free CME! Join the TB coalition h t t p : / / publichealth.lacounty.gov /tb/coalitiontoendtb.htm LA County TB infection toolkit for providers h t t p : / / publichealth.lacounty.gov /tb/providertoolkit.htm 15