Case Presentations

1. Case Presentations Adrian Gardner MD, MPH Clinical Research Fellow Miriam Hospital/Alpert School of Medicine at Brown University May 1, 2010

2. 24 yo F from Liberia  US in 1999 PMH: HIV (dx 2004), CD4 350-400, VL ND on ARVs LTBI (TST 24 mm) s/p INH (2002)- ? Poor adherence Annual trips to Liberia Asthma h/o RUL PNA (2/08) clinically improved w/ moxifloxacin x 7d 8/08: Developed cough, fever x 5 days Called PCP, started on moxifloxacin Few days later, pursued “follow-up” CXR Case 1

3. Case 1

4. Case 1 • Admitted to hospital for further work-up • Exam: T 102 HR 80-120 wt 126 lbs O2 sat: 99% RA • Bronchial BS anteriorly on right side 6 12 5.3 189 1.0 36 AST: 18 ALT: 11 N:61 L:25 M:13 E:0.5 Bas:0.2

5. Case 1 • Hospital course: • CT scan: dense consolidation RUL with septated cavity, no LAD • Antibiotics changed to CTX/Clindamycin • Unable to produce sputum • Bronchoscopy performed • BAL: AFB smear + • Started on Rifabutin/I/Z/E

6. 33 patients in Baltimore, MD with culture-confirmed TB • 16 (48%) had received FQ for CAP before TB diagnosis • Of these 16, 83% improved clinically within ~ 3 days. 10 were discharged from hospital prior to TB diagnosis being made. • Median time until re-presentation and initiation of TB treatment was 5 days in those who did not receive a FQ vs. 21 days in those who did (p=0.04) • Initial empiric treatment with FQ is associated with delay in initiation of appropriate anti-TB treatment.

7. 640 pts in TN with culture-confirmed TB (2002-2006) • 116 (18%) had FQ exposure in 12 months prior to TB diagnosis • 16 (2.5%) isolates were FQ resistant • FQ exposure >10 days was associated with FQ resistance (OR= 7.0, p= 0.001) and highest risk if exposed >60 days prior to TB diagnosis (OR= 17, p < 0.001)

8. Seen in TB clinic BAL (8/7/08) and sputum cx grew MTB Placed under quarantine 9/08: Lab reports difficulty with DST Prelim results: Resistance to I/Z Low level resistance to E Specimen sent to CDC for 2nd line DST Case 1

9. Case 1 Cough improved Sputum smears neg CXR unchanged • What would you do? • Re-assess clinically • Continue current meds until DST results final • d/c I/Z, add FQ, injectable (Rifabutin/E/FQ/AG) • d/c all, change to Ethio/AG/FQ/Cycloserine/PAS • Worry about Rifabutin, FQ resistance • Seek help!

10. 9/12/08…..d/c I/Z, E dose increased, add FQ, injectable (Rifabutin/E ( )/FQ/AG) Four days later, lab reports… Resistance to I, Z, low dose E Sensitive to R/SM (initial isolate) 11/08: sparse growth on cx specimens from 8/24/08, 9/21/08 Identification not possible 12/08: CDC reports specimen “contaminated” request new isolate Case 1

11. Case 1 • 1/09 • CXR improved • Specimen from 8/24 reported as pan-S MTB • CDC reports 2 mycobacteria • Confirms pan-S MTB • Unable to grow #2 • 2/09 • 6 months tx complete • Rifabutin/I/FQ x 3 mo • 5/09 • Completed therapy • Q 6 mo surveillance • 8/09 • Pregnant!

12. Case 1: Take Home Points • Use of FQ to treat respiratory or other infections in patients with undiagnosed TB leads to delays in starting TB treatment and FQ resistant TB. • When TB is on the differential, consider another drug for treatment of community acquired pneumonia • Always talk directly with the lab—the lab is your friend! • Consider the possibility of a mixed/complex mycobacterial infection

13. Case 2 • 20 year old Caucasian, female University Student • PMH significant for anorexia nervosa 4 yrs ago, recent wisdom teeth extraction • Has lived in New Zealand in the past • Two years ago, spent 3 months living with host families in Yunan Province, China as part of a student exchange program • Last year, traveled to Thailand, Japan for 2 weeks • No known TB contacts, never had a PPD in past. • June, 2009: PPD placed prior to starting volunteer, research position at VA hospital. PPD 30 mm. She reported no symptoms.

14. Case 2: CXR

15. Case 2 • Sputum smears negative • Started on R/I/Z/E • Sputum cx grew TB

16. Case 2: Take Home Point • Students/volunteers/health care workers spending time in TB endemic areas of the world should receive counseling about: • the risks of TB exposure • strategies for minimizing exposure • signs and symptoms of active TB • the importance of pre and post-travel testing for LTBI

17. 41,168 people who sought medical advice after recent travel • Risk of latent TB infection • Short-term: 4/1000 • Long-term: 11/1000

18. Peace Corp Epidemiologic Surveillance System 1996-2005 • 44,070 volunteers • 801,780 volunteer-months • 1028 PPD conversions • 46 cases active TB • Overall rate: 68.9 per 100,000 • Conversion rates (conv/ vol-mo): • Africa region 1.467 • Central America 1.272 • Caribbean 0.994

19. Rates of TB infection in students, trainees in an academic, international medical exchange program(Adrian Gardner, E. Jane Carter) • Survey of 400+ travelers to Western Kenya (2004 – 2009)

20. Methods and Preliminary Results • Survey program participants who traveled to Eldoret, Kenya in association with the AMPATH program between July, 2004 – June, 2009 • Administered questionnaire via an online survey tool and by hard copy upon request • 69% responded (N=418) • Analysis in progress

21. Results: Demographics

22. *Other- PCP, Health center, previous travelers, self

24. Other includes safari trips, downtown restaurants/dance clubs, classrooms, weddings, operating room, pharmacy,TB clinic

26. 47% 41% 9%

27. Revealing Comments…. • “I visited AMPATH, but was not involved in any of the TB work. Just wanted you to know that I will not be completing the survey.” • “I don't think I should be on this list. I took a short mission trip to Kenya but I know nothing about the TB testing. I do not remember any council specific to TB before we left, just general information about immunizations but the discussions focused more on malaria.” • “I work with SMILE providing laboratory support. The survey does not really apply to my experience in Eldoret. Therefore, I did not fill in the survey.”

28. Results: “Ideal care” • Definition of “Ideal Care” • Pre-travel counseling on TB • Pre-travel TST within one year of departure • Post-travel TST related to travel • Only 28% of adult participants received “ideal care” (i.e. met all three criteria)

29. Results: TST conversions • 10 participants reported a negative pre-travel TST and + TST post-travel for a conversion rate of 2.7 - 3.8%. • Of those who reported TST conversion or active TB, 8 (3.2%) reported participation in direct medical care vs. 3 (1.6%) reported no participation in direct medical care. • One participant reported active TB • 66 children under the age of 21 years accompanied survey respondents to Kenya. • Of these, 26 (39%) had a TST upon return and 3 had a conversion for a conversion rate of 4.5% - 11.5%.

30. Rates of TB infection in students, trainees in an academic, international medical exchange program • HCW and students are not receiving the pre-travel counseling they need • Participants, especially non-HCW do not perceive their risk • Program participants are not getting adequate pre-travel/post-travel screening

31. Case 2: Clinical Course • She reports that the risk of TB was not discussed prior to her trip to China • Hepatotoxicity requiring discontinuation of PZA • Currently on R/I and tolerating well

32. Case 2: Take Home Point • Students/volunteers/health care workers spending time in TB endemic areas of the world should receive counseling about: • the risks of TB exposure • strategies for minimizing exposure • signs and symptoms of active TB • the importance of pre and post-travel testing for LTBI “Targeted testing” should include these individuals

33. 36 yo F from Rhode Island Referred to TB clinic in 2006 with +TST (22 x 22mm) done with pre-natal screening Father was from Cape Verde and had a history of TB in 1992 in RI. She was contact and had negative TST at that time. She also reported neg TST in 1997 when she worked at a homeless shelter Works in RI, no travel outside US CXR: normal Case 3

34. Case 3 • Per protocol, LTBI therapy was deferred until post-partum • Scheduled for visit 3 mo post-partum • DNKA appt on 1/5/07, 2/1/07, 4/13/07. Per clinic protocol, memo sent back to her referral site and DOH.

35. Case 3 • 2009- She is referred to TB clinic after a LN biopsy reveals…… • NECROTIZING GRANULOMATOUS LYMPHADENITIS • Special stains are NEGATIVE for mycobacteria (AFB, Fite) and fungal organisms (GMS, PAS) • Cx of LN grew MTB (pan-susceptible) • What happened between 2006-2009?

36. Case 3 • July, 2006: She developed proteinuria during her pregnancy and HIV test performed during that work-up revealed that she was HIV+ (30 wks pregnant) • CD4 201, VL 101,372 • Started on ARVs, followed closely in HIV clinic viral load undetectable • Sept, 2006: Delivered healthy baby boy

37. Case 3 • Continued ARVs until August, 2007 then stopped and lost to follow up • March, 2008: Returned to HIV clinic but never re-started her ARVs • April, 2009: Returned to HIV clinic with 1 month history of fever, cough which resolved with azithromycin and prednisone. • Re-started on ARVs

38. Case 3 • April, 2009: • Admitted with watery diarrhea, nausea • no vomiting but unable to take meds, ARF • CT Abd/pelvis: • Extensive RP lymphadenopathy • Lymph node biopsy was performed • Started on moxifloxacin with improvement in fever, diarrhea

39. Case 3

40. Case 3 • Pathology • NECROTIZING GRANULOMATOUS LYMPHADENITIS • Special stains are NEGATIVE for mycobacteria (AFB, Fite) and fungal organisms (GMS, PAS)

41. Case 3 • June, 2009 • Cx of LN grew MTB (pan-susceptible) • Started on TB therapy

42. Case 3 • What went wrong between 2006-2009? • Missed opportunity • Better communication between providers/clinics • Patient kept her appointments • Someone in HIV clinic- thought about TB • Someone in TB clinic- thought about HIV

43. HIV testing in TB clinic • HIV testing of active TB patients • What about patients with LTBI? • CDC guidelines (2006) recommend opt-out HIV testing in all health care settings

44. Extended back-calculation model to estimate the prevalence of undiagnosed HIV in US • Demographic and behavioral groups

46. Rapid HIV testing in TB clinic • Pilot of opt-out HIV testing for all LTBI patients

48. Case 4 • 21 year old M presented to the emergency room with a six month history of neck pain and headaches. • Over the last two weeks prior to admission he had worsening neck pain now with limited mobility. No trauma. He notes history of both fevers and chills but has not taken his temperature. • 40 pound weight loss over 6 months. • No cough, sputum production, chest pain, nausea, vomiting, anorexia.

49. Case 4 • Denies stumbling, weakness or loss of bowel or bladder control • He has no past medical problems and is on no medications • He was born in Guatemala and has been in the US for two years. He works as a landscaper (heavy lifting and physical activity) • No known history of exposure to TB. He has no animal exposure including domestic cats. He neither smokes nor drinks alcohol • Lives with his brother. Denies any sexual partners

50. Case 4 • Physical Examination: • T 99 HR 109 BP 136/82 • Gen: Uncomfortable due to neck pain • HEENT: Unremarkable except limited range of motion of his neck. Moderate tenderness diffusely over the posterior neck, no discernable mass or adenopathy • Chest: clear to auscultation bilaterally • Neurologic: alert and oriented. Cranial nerves II-XII were intact. Sensation intact to light touch and pinprick throughout. Reflexes 2 + (biceps, triceps, patellar and Achilles). Normal rectal tone.