Tuberculosis

1. Introduction to Public Health/Communicable Diseases/Tuberculosis Tuberculosis An Old Disease – New Twists A Continuing Public Health Challenge Jane Moore, RN, MHSA Director, TB Control & Prevention Program - VHD, 2013

2. Tuberculosis – Old Disease • May have evolved from M bovis; acquired by humans from domesticated animals ~15,000 years ago • Endemic in humans when stable networks of 200-440 people established (villages) ~ 10,000 years ago; Epidemic in Europe after 1600 (cities) • 354-322 BC - Aristotle – “When one comes near consumptives… one does contract their disease… The reason is that the breath is bad and heavy…In approaching the consumptive, one breathes this pernicious air. One takes the disease because in this air there is something disease producing.”

3. Tuberculosis • 1882 – Robert Koch – “one seventh of all human beings die of tuberculosis and… if one considers only the productive middle-age groups, tuberculosis carries away one-third and often more of these…”

4. M tuberculosis as causative agent for tuberculosis Robert Koch 1886

5. TB as a Worldwide Public Health Issue • World population ~ 6 billion • ~ 1in 3 people in world infected • ~ 9.4 million new cases of active TB/year • 1.7 million deaths/year • US population 280 million • ~ 3-5% infected • Now < 10,000 cases/year • ~ 5-7% mortality

6. TB in the US – 1882-2012 • 1900-1940 TB rates decreased in the US and Western Europe before TB drugs available • Better nutrition, less crowded housing • Public health efforts • Earlier diagnosis • Limit transmission to close contacts • TB sanatoria • Surgery

7. TB in the US – 1882-2012 • 1940s-1960s TB specific antimicrobial agents • Single drugs – use produced resistance • Multiple drugs • 1960s-1980s TB considered a non-problem • TB treatment moved to private sector • Loss of TB-specific public health infrastructure

8. TB in the US – 1882-2012 • 1990s TB re-emerges as a threat • TB-HIV co-infection • Drug-resistant TB • Globalization allows TB to travel • 1990s Increased support for TB prevention and control • Funding for public health efforts (case management, contact investigation, directly observed therapy • Better diagnostic and patient management tools • 2012 • Lowest number of reported cases in US - <10,000

9. TB Around the World • One-third of the world is infected with TB, an average of one new infection per second • Two million people died from tuberculosis in 2010, 1 every 20 seconds • TB is the leading killer of those with HIV • TB is the 2nd leading killer from an infectious disease

10. Global TB Incidence Rates *2011 *Estimated

11. TB in Virginia: 1990-2012 235

12. Virginia TB Cases - 2012 Race and Ethnicity Place of Origin

13. TB Case Rate per 100,000 VA and US: 2007-2012

14. VA TB Cases by Region: 2007-2012

15. TB: Airborne Transmission

16. TB Invades/Infects the Lung Effective immune response Infection limited to small area of lung Immune response insufficient

17. TB – A Multi-system Infection

18. Natural History of TB Infection Exposure to TB No infection (70-90%) Infection (10-30%) Latent TB (90%) Active TB (10%) Never develop Active disease Untreated Treated Die within 2 years Survive Die Cured

19. Latent TB vs. Active TB Latent TB (LTBI) (Goal = prevent future active disease) = TB Infection = No Disease = NOT SICK = NOT INFECTIOUS Active TB (Goal = treat to cure, prevent transmission) = TB Infection which has progressed to TB Disease = SICK (usually) = INFECTIOUS if PULMONARY (usually) = NOT INFECTIOUS if not PULMONARY (usually)

20. Treatment • Most TB is curable, but… • Four or more drugs required for the simplest regimen • 6-9 or more months of treatment required • Person must be isolated until non-infectious • Directly observed therapy to assure adherence/completion recommended • Side effects and toxicity common • May prolong treatment • May prolong infectiousness • Other medical and psychosocial conditions complicate therapy • TB may be more severe • Drug-drug interactions common

21. TB – continues as a public health issue in the United States • Old public health concepts (isolation of infectious individuals, closely monitored treatment, recognition and preventive treatment for infected contacts,) are still critical, but will not eradicate TB • Care providers not familiar with signs/symptoms of TB • Diagnosis delayed • Inappropriate treatment • Drug resistance due to improper use of drugs • Must address both US born and newcomer populations • Older, remote exposure • Incarcerated, homeless, history of drug , alcohol use • Newcomers from high TB prevalence areas

22. Challenges to Public Health System • Public health workers must: • Educate, coordinate care with private sector • Identify support services (food, housing) • Treat TB in geriatric populations • Treat TB in children • Deal with alcohol, drug abusing, incarcerated and/or homeless patients • Manage TB in patients with underlying medical conditions • Provide culturally appropriate care for non-English speaking/non-literate populations • Treat TB cases with drug- resistant TB

23. Addressing the Challenges – TB Control in the US - 2012 • Local, state and federal programs have separate but closely related activities • Guidelines, Laws and Regulations • Guidelines – treatment, contact investigation, prevention – data driven/expert opinion • Laws – local or state – case reporting, isolation of infectious individuals • Regulations - local or state – implement laws • Federal laws/regulations – travel restrictions, entry into the US – no interstate restrictions • International travel regulations – WHO – limited

24. Elements of a Tuberculosis Control Program X-ray Targeted testing/ LTBI treatment Clinical Services Pharmacy Inpatient care Medical evaluation and follow-up Laboratory Non-TB medical services Social services HIV testing and counseling Interpreter/ translator services Occupational health, school, jail, shelter, LTCF screening Patient education Data collection Coordination of medical care Documentation Epidemiology and Surveillance Home evaluation Contact investigation Case Management DOT Outbreak Investigation Data analysis Housing Program evaluation & planning Isolation, detention Follow-up/treatment of contacts QA, QI for case management Consultation on difficult cases Data for local, state, national surveillance reports Training Federal TB Control Program State TB Control Program Guidelines State statutes, regulations, policies, guidelines Information for public Funding National surveillance Training Technical assistance Funding VDH/DDP/TB Jan 2007

25. VDH TB Prevention and Control Policies and Procedures • Based on USPHS/CDC, ATS, IDSA and Pediatric “Red Book” guidelines • Adapted to address uniquely Virginia issues

26. DDP TB Prevention and Control Activities • Core activities • Identification and treatment of TB cases • Identification, evaluation and treatment of high risk close contacts of cases • Surveillance/case reporting • TB laboratory services • Targeted testing and LTBI treatment for high risk populations • Training/continuing education for health care providers • Program evaluation

27. TB Control provided funding for TB-related activities at Local Health Departments • PHN/ORW/Epi Reps (VDH/DDP employees and contracts) • TB clinic physicians (contracts) • Chest x-rays and laboratory tests • TB medications for uninsured case patients • Incentives and enablers • Training for HDs, PHNs, ORW

28. Services directly provided by Central Office (Richmond) • Case reporting, surveillance activities • Site visits to review case records, collect data • Data entry/management/analysis/reports • Feedback to local health departments • Data for national TB surveillance system • Information for local/state/federal government officials

29. Services directly provided by Central Office • Technical support/consultation • Case management • Contact investigations • Expert clinical consultation available through partnerships with EVMS and UVA • Case review conferences (QA, QI) • TB prevention/control in congregate living facilities, health care facilities

30. Services provided by Central Office • Educational activities for public and private sector HCPs, patients and the public • VDH conferences for public health workers • Speakers at private sector HCP meetings • Distribution of guidelines • Website

31. Currently Available Laboratory Services • DCLS • Standard TB Bacteriology • Smear, DNA Preliminary Culture, Standard Culture, Susceptibility • Molecular testing • MTD – Mycobacterium tuberculosis Direct • Cephid testing in validation process

32. Currently Available Laboratory Services • Other Laboratories • Florida State Laboratory • HAIN testing – molecular susceptibility for INH/RIF • Centers for Disease Control and Prevention • First and second-lined molecular drug susceptibility testing • Genotyping of isolates • University of Florida Pharmacokinetics Laboratory • Serum drug level testing

33. Current Programmatic Initiatives • Statewide availability of Interferon Gamma Release Assay for testing for latent TB infection • Blood test • 2 commercial products • QuantiFeron Gold InTube • T-Spot-TB – Chosen for Virginia for logistical reasons

34. Current Programmatic Initiatives • New Treatment for latent TB infection (LTBI) • 12 week course of isoniazid and rifapentine (3HP) • Virginia Guidelines document developed • Pros • Shortens treatment course from 9 months to 12 weeks • Weekly instead of daily or twice weekly treatment • Cons • Requires directly observed treatment – observe dose ingestion • Costly – but price is coming down • Number of pills – but new formulations under development

35. Current Programmatic Initiatives • Routine serum level drug testing of all diabetic TB cases early in treatment • A study of slow to respond to treatment TB cases showed statistical significance for diabetes • Pilot demonstrated high percentage of diabetics had low serum levels for TB drugs • Next phase – impact on sputum conversion • Goal • Shorten infectious period and potential for community transmission • Shorter treatment duration with resulting lower cost

36. Programmatic Initiatives • Increased focus on contact investigation activities • Monitoring ongoing evaluation of contacts, especially children and immunocompromised contacts • Monitoring treatment of infected contacts

37. Programmatic Initiatives • Focus on program evaluation activities • Ongoing case reviews of current cases • Cohort Review of prior year cases for 6 selected national indicators • Completion of treatment, HIV testing, Sputum collection, sputum conversion, susceptibility results, and initiation of treatment with 4 anti-TB drugs • District program review and record audit

38. Current Needs for TB in the US • General • Continued support for TB prevention/control especially with health care reform • Sequestration and future federal budget reductions will have impact • New drugs and/or drug combinations to allow shorter courses of treatment • New drug bedaquiline approved by FDA • Use limited to multi-drug resistant pulmonary cases who cannot be treated with other drugs

39. Current Needs for TB in the US • Shorter, simpler, less expensive treatment regimens • Vaccine (beyond BCG) • Still waiting • Support for global TB prevention and control activities • Federal funding reductions for global TB activities

40. Current Needs for TB in the US • Reliable access to anti-tuberculosis drugs • Isoniazid – ongoing national shortage since Fall 2012 • Use in Virginia now limited to certain persons • PPD Solution – not a diagnostic – classified as a Schedule VI drug in Virginia • Started as national shortage of Tubersol, now spread to alternative product , Aplisol • Multiple injectible agents used for drug resistant TB in short supply • National shortage for several years

41. Assessing the Impact • TB currently at lowest number and rate for both US and Virginia since records kept • Current drug shortages have the potential to hamper further progress in TB control and elimination • Priority on identifying and treating contacts to known cases • Using T-Spot.TB for testing contacts > age 12, skin test for younger children • Using isoniazid and rifapentine to treat contacts • Isoniazid sparing regimen • Others at high risk – testing & treatment deferred

42. Thank you Questions? Jane Moore Jane.moore@vdh.virginia.gov 804 864 7920