Treating Tuberculosis in Indian Country

1. Treating Tuberculosis in Indian Country Jonathan V Iralu, MD, FACP Navajo Area Indian Health Service Infectious Disease Consultant

2. Navajo Culture • The Dine are a tribe who speak a language related to Apache and the Athabascan languages of Canada and Alaska. • They have an ancient, rich and beautiful culture and live in the American Southwest in the four corners region (Arizona/New Mexico/ Colorado/ Utah)

3. Navajo Cosmology • Navajo origin stories point back to an emergence from four previous worlds into this, the Glittering World. • First Man and First Woman were created by the Holy People, supernatural beings who taught The Dine how to survive in a world full of both beauty and danger.

4. Navajo Cosmology • Religious practice focuses on restoring health and ensuring survival. • By following the rules, one stays safe • Navajos were taught the healing ceremonies by the Holy People • The ultimate goal is to restore “Hozho” or balance

5. 3 causes of sickness for the Diné • Retribution from the Holy People for a broken taboo (lightning, snakes, etc) or omission (not thinking and speaking positive) • Contact with ghosts- the malignant part of a dead person • Witches- malevolent people place a curse on the patient and they fall ill

6. Navajo Medicine • Diagnosis is made by a diagnostician • Star gazing • Crystal gazing • Hand Trembling • Cures are made by a Singer who performs a ceremony: • Singing • Sand painting • Prayers • Herbal medicine

7. Navajo MedicineTreatment:Ceremonials • Holy Way Chants • Beauty Way snake cure • Shooting Way lightening cure • Mountain Top Way bear cure • Life Way Chants bodily injuries • Evil Way Chants ghost sickness

8. Navajo MedicineTreatment:Ceremonials • Tuberculosis: • Navajo word for Tb, jei di means “disappearing heart” • Tb is caused by contact with lightning-struck wood • Cured by the shooting way ceremony by a medicine man who is expert in this ceremony • The whole goal is to achieve harmony

9. Navajo History • Early Period: prior to 1626 • Lived in Dinetah with an agrarian lifestyle • Spanish Period (1626-1846) • Spanish took Pueblo land and Navajos migrated West. • American Period (1846- ) • Attacked by General Kearney • Barboncito, Manuelito Zarcillos Largos boldly resisted • Kit Carson in 1863 ordered to destroy their land

10. Navajo History Western anthropologist’s view: • Under Carson’s attacks, Navajos starving by1864 . • Ordered to surrender at Fort Defiance and forced on Long Walk 300 miles south east to Ft. Sumner • Chiefs Manuelito and Barboncito resisted capture • Remainder were forced to farm unfamiliar crops in poor soil.

11. Navajo History and Tuberculosis • Yellow Fever and Cholera plagued the Navajo at Ft Sumner. • Upon return to Dinetah, the first US government physician noted “consumption” among the Navajo. • By 1912, 10% of the Diné had TB & TB was responsible for 50% of all illness seen on Navajo

12. Navajo History and Tuberculosis “the Indian office was collecting and taking children off to non-reservations schools. It was a terrible mistake for they began returning and dying of TB. I had no place to keep them.” -an early physician

13. Navajo History and Tuberculosis • In 1925 25% of reservation deaths were due to Tb. • Hospital opened at Ft Defiance 1938: • 343 Tb patients 230 deaths. • Chairman Chee Dodge petitioned the federal government to intervene but congress focused spending on off reservation treatment of Navajos.

14. Navajo History and Tuberculosis

15. Navajo History and Tuberculosis • Cornell physicians under Walsh McDermott began INH trials on Navajo in the early 1950’s • The Many Farms Demonstration Project • “Comprehensive Community Health Care” • Utilized Navajo “Home visitors”- the precursors to the modern TB technicians and Community Health Reps

16. Navajo History and Tuberculosis Annie Wauneka • Daughter of Chee Dodge & only woman on tribal council in 1951 • Studied Tb for 4 months at the Ft Defiance Tb San to learn about “the little red worms” • Visited Navajos in TB Sans in the 4 corners region • Did home visits to teach her people about the “bugs that eat the body” (the Badge Lady)

17. Navajo History and Tuberculosis • Annie Wauneka’s accomplishments • The discharge against medical advice rate on Navajo dropped dramatically by 1954 through her teaching • She taught the Navajo medicine men about TB • Created the “health visitor” program of Many Farms- precursor of our current DOT TB treatment model • Advocated for transfer of Indian health from the BIA to the US PHS through the IHS

18. Navajo Nation/IHS TB Program • In 1972 the Navajo Nation and the Navajo Area IHS began a collaboration to treat TB on the Navajo Nation using bilingual Tb workers who • administer DOT • complete contact investigations in Navajo • Monitor Tb screening on the reservation

19. The barrier of poverty….

20. Latent TB Infection • Who to treat --do not treat every positive PPD. • Only treat those with these risk factors: • Patients at risk for spreading TB • Patients at personal risk for reactivating TB

21. Latent TB Infection • Patients at risk for spreading TB • Health Care Workers with direct patient contact (doctors, nurses, radiology and lab techs, custodians, food services, clinic secretaries, etc) • School Employees with student contact (teachers, cafeteria workers, school bus drivers, etc) • Residential facility employees and residents (nursing homes, group homes, jails, detox centers, shelters, etc)

22. Latent TB Infection • Patients at personal risk for reactivating TB • 5 mm PPD cutoff: • HIV positive • Contact of active TB case • Fibrosis on CXR consistent with healed TB • Immunosuppressed (>15 mg prednisone/d for >1 month, transplant, infliximab, etc) • 10 mm PPD cutoff: • Recent immigrant • IDU • Resident or HCW at jail, nursing home, hospital, shelter • DM, CKD, lymphoma/leukemia, weight loss, silicosis, gastrectomy, age < 4years old, ALD

23. Latent TB Infection • Important Reminders: • Don’t test and don’t offer treatment for people with no risk factors. • Symptomatic patients or those with abnormal CXR suggesting TB need 3 negative sputum cultures before treatment for latent TB. • Ignore the old age cut-off of 35 years.

24. IGRAs • Interferon Gamma Release Assays • Measure release of IFN-g in response to Tb Ags (ESAT-6 and CFP-10) • T-Spot • Sensitivity 96% • Specificity 99% • Quantiferon Gold (ESAT-6, CFP 10) • Sensitivity: 87% • Specificity: 99% • Not affected by BCG

25. IGRA’s • Uses: • Contact investigation • Evaluating Immigrants who had BCG • Screening HCW’s and Residential facility residents annually • All other settings where PPD is used for screening • Limitations: • Recent exposure, immunocompromised, age <17

26. How to treat Latent TB • Preferred Adult Regimens: • INH 300 mg po daily for 9 months • Rifampin 600 mg po daily for 4 months • INH can be given 900 mg po 2 or 3 times a week as DOT (dialysis, institutionalized, other high risk patients)

27. How to treat Latent TB Important Reminders: • Supplement INH with pyridoxine 50 mg po daily • Rifampin cannot be given intermittently like INH • INH is first drug of choice for most patients, Rifampin is a second choice and might be reserved for the patient with pre-existing hepatitis

28. How to treat Latent TBMonitoring for toxicity • Monitor the patient for symptoms of toxicity and physical exam monthly • INH: rash, neuropathy, N/V, anorexia, jaundice, lupus-like illness • Rifampin: rash, , flu-like illness, jaundice, bleeding • Monitor the LFT’s monthly on INH and the LFT’s and CBC monthly on Rifampin • INH: transaminitis • Rifampin: cholestasis, thrombocytopenia, leukopenia

29. Active TBInitial Evaluation • Admit to the hospital • Place on Airborne Isolation • Collect 3 sputa for AFB in the first 24 hours including one early morning sputum. • Start anti-TB therapy within 24 hours if TB is strongly suspected • Obtain an HIV serology and viral hepatitis panel on every case

30. Nucleic Acid amplification tests • Two tests: • E-MTD: isothermal amplification16S ribosomal gene • Amplicor: PCR of 16S ribosomal gene • > 95% sensitive is smear positive • 60-90% if smear negative • Interpretation: • If NAA test positive: treat for TB and contact investigate • If NAA test is negative, TB is not definitively ruled out

31. Nucleic Acid drug resistance testing • Rifampin resistance: • detect mutations in rpo gene of MTb • Sensitivity 0.98, specificity 0.99 • INH resistance • Sensitivity 0.83, specificity 1.00

32. Active TBInitiation of treatment • Treat all NAIHS Patients with 4 drugs: INH,Rifampin, EMB, PZA • Treat 2 weeks in the hospital with daily therapy to monitor response and labs • Continue for 6 weeks with 4 drugs always with home based DOT

33. Active TB • When to simplify the regimen: • Stop EMB as soon as the culture results show sensitivity to the other 3 drugs • Stop PZA when 8 weeks of therapy are completed

34. Active TB- Continuation Phase • 6 months total with INH and Rifampin if: • cultures collected at 8 weeks are subsequently negative • there were no cavities on the CXR • 9 months of INH & Rifampin if: • there were cavities on the first CXR and • the week 8 culture is positive • Always use DOT for the duration!

35. Active TB- Monitoring Response • Monitor for treatment success by • checking a monthly sputum for AFB smear and culture for the duration of therapy and at completion • Obtain a follow-up chest x-ray at 2 months and at the completion of therapy.

36. Active TB- Monitoring for Toxicity • Monitor for INH and Rifampin toxicity as we did for the LTBI patient • Monitor for EMB toxicity with a baseline color vision test and repeat as needed • Monitor for PZA toxicity by following for hepatotoxicity, rash and gout

37. Active TB- Managing Hepatotoxicity • Monitoring: • Check LFT’s 2-3 x per week in the hospital • Check LFT’s and CBC monthly in the clinic • When to interrupt therapy: • Stop INH, RIF, PZA but continue EMB if the ALT and AST are 5 times greater than normal regardless of symptoms. • Stop INH, RIF, PZA but continue EMB if the ALT and AST are 3 times greater than normal and the patient has symptoms

38. Active TB-Managing Hepatotoxicity • When LFTs normalize (<2x ULN), re-challenge sequentially: • INH daily for 3 days then • change to Rifampin daily for 3 days then • change to PZA daily for 3 days. • Check LFT’s daily. • Call for infectious disease consultation in the event of toxicity to construct a new regimen

39. Extrapulmonary TB • Sites of involvement • Meningeal • Pleural • Pericardial • Bone/Joint • Renal/Testicular • Skin • Ophthalmic • Miliary

40. Extrapulmonary TB • Diagnosis • Pleural: VATS vs percutaneous Bx, ADA, PCR • Miliary: Bone Marrow or Liver Biopsy • Renal : Urine Culture/CT scan • Bone: Bone biopsy

41. Extrapulmonary TB • Treatment • Use conventional 4 drug therapy • Bone TB: 12 months • TB Meningitis: 9-12 months • All others: 6 months

42. Active TB- Contact Investigation • Test all family and social circle contacts with a PPD skin test • Repeat PPD testing at 8-10 weeks on all contacts who are initially PPD negative • Get CXR’s on the close home contacts to rule out active TB

43. Active TB- Contact Investigation • Offer INH to the PPD positive (greater than 5 mm) adults and children who have not been treated for latent TB before • Offer INH to PPD negative children less than 5 years old with a clear CXR. Repeat the PPD at 12 weeks and if PPD negative stop INH. • Offer INH to HIV positive or other substantially immune-compromised contacts even if PPD negative.

44. How to run a NAIHS Chest Clinic • Regularly schedule 1 – 2 Chest clinics per month • Always run the chest clinic in conjunction with the service unit Navajo Nation TB program TB technician

45. How to run a NAIHS Chest Clinic • The TB technician should: • check that the appropriate blood work has been drawn • perform a screening review of symptoms • estimate the degree of adherence • Make phone calls or home visits to all patients who miss appointments • Give DOTto all cases of active TB and tohigh risk Latent TB patients such as dialysis patients or HIV positive patients.

46. How to run a NAIHS Chest Clinic • The Chest Clinic clinician should • Monitor for signs and symptoms of toxicity • Check the LFT’s and CBCs that are ordered • Review the duration of therapy at each visit eg. “5 of 9 months of INH completed” • Carefully document when treatment for TB is completed in the EHR or paper problem list to avoid confusion in the future.

47. Court Orders • Patients with active pulmonary TB are considered a public health risk and can be court ordered to get treated. • Draft a petition with your TB Technician and the technician or you can present it to a Navajo Nation court. • Get permission from Area Office if you are asked to speak to the judge • Admit to a NAIHS hospital if not MDR and keep the patient until they get the message. • Refer to a locked-up ID hospital if the patient does not get the message

48. Navajo Nation Tb Program Impact • 100% of active TB cases receive DOT • Diabetics are the main focus of DOPT on Navajo • The TB incidence for 2005 was equal to US all races.