Case Presentations

Adrian Gardner MD, MPH

Clinical Research Fellow

Miriam Hospital/Alpert School of Medicine at Brown University

May 1, 2010

Case 1

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

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

5.336

N:61 L:25 M:13 E:0.5 Bas:0.2 AST: 18

ALT: 11

12189

6

1.0

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

• 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.

• 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)

Case 1

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

What would you do?

a) Re-assess clinically

b) Continue current meds until DST results final

c) d/c I/Z, add FQ, injectable (Rifabutin/E/FQ/AG)

d) d/c all, change to Ethio/AG/FQ/Cycloserine/PAS

e) Worry about Rifabutin, FQ resistance

f) Seek help!

Cough improved

Sputum smears neg

CXR unchanged

Case 1

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

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!

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

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.

Case 2: CXR

Case 2

Sputum smears negative

Started on R/I/Z/E

Sputum cx grew TB

Case 2: Take Home Point

Students/volunteers/health care workers spending time in TB endemic areas of the world should receive counseling about:

1) the risks of TB exposure

2) strategies for minimizing exposure

3) signs and symptoms of active TB

4) the importance of pre and post-travel testing for LTBI

• 41,168 people who sought medical advice after recent travel

•Risk of latent TB infection

•Short-term: 4/1000

•Long-term: 11/1000

Travel time %

< 1 month 60%

1-6 months 30%

> 6 months 10%

• 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

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)

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

Results: DemographicsAge (years)

18-21

22-30

31-40

41-50

51-60

>60

N (%)

6 (1.4)

167 (40.3)

110 (26.6)

57 (13.8)

53 (12.8)

37 (8.9)

Gender

Female 227 (54.8)

Medical History

No chronic medical illness 340 (93.4)

TB History

Negative test for LTBI

History of LTBI

Never tested for LTBI/Unknown

326 (80.5)

36 (8.9)

43 (10.6)

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

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

47%

41%

9%

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.”

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)

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%.

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

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

Case 2: Take Home Point

Students/volunteers/health care workers spending time in TB endemic areas of the world should receive counseling about:

1) the risks of TB exposure

2) strategies for minimizing exposure

3) signs and symptoms of active TB

4) the importance of pre and post-travel testing for LTBI

“Targeted testing” should include these individuals

Case 3

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

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.

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?

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

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

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

Case 3

Case 3

Pathology– NECROTIZING GRANULOMATOUS

LYMPHADENITIS – Special stains are NEGATIVE for

mycobacteria (AFB, Fite) and fungal organisms (GMS, PAS)

Case 3

June, 2009– Cx of LN grew MTB (pan-susceptible)– Started on TB therapy

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

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

Extended back-calculation model to estimate the prevalence of undiagnosed HIV in US– Demographic and

behavioral groups

Rapid HIV testing in TB clinic

Pilot of opt-out HIV testing for all LTBI patients

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.

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

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.

10.236.2

N:85 L:8 M:6.0 E:0 Bas:0 AST: 18

ALT: 14

AP: 66

T. bili: 0.7

12.6383

13

0.7

Case 4

Case 4

CXR: Clear lung parenchyma, suggestion of a paratracheal soft tissue density on the right and left hilar fullness

Cervical spine x-ray: unremarkable 

Case 4

Case 4

Admitted to the hospital for pain control and diagnostic work-up.  – ENT consulted and an US-guided biopsy of pharyngeal mass was performed from a posterior

approach. Specimens were collected for cytology and revealed necrotizing granulomatous inflammation with no sign of malignancy, gram stain/AFB stain negative.

– TST positive, HIV negative

– Sputum smear neg x 3, BAL smear neg. Given the patient’s background, the diagnosis of tuberculous osteomyelitis with mediastinal adenitis and retropharyngeal abscess was considered to be most likely. The patient was started on four drug anti-tuberculous therapy with Isoniazid, Rifampin, Pyrazinamide and Ethambutol.  

Two and a half weeks later, the biopsy specimen, BAL fluid, and all three sputa grew Mycobacterium tuberculosis. 

Diagnosis: TB osteomyelitis of C1-2 with retropharyngeal abscess and intrathoracic nodal involvement.

TB Vertebral Osteomyelitis

Pott’s disease– 1-2% of TB cases

Many case series re: role of surgery– Debridement vs. debridement + stabilization

Cochrane Review– Routine surgery in addition to chemotherapy for treating

spinal tuberculosis (2010)

Outcomes– Mortality, TB cure– Kyphosis angle, neurologic deficits, pain, bone loss, activity level

TB Vertebral Osteomyelitis

Debate goes back to 1960s

Possible indications for surgery– Non-diagnostic biopsy – Neuro deficit caused by cord compression– Spinal instability caused by destruction of

vertebrae or kyphosis > 30°– No response to chemotx– Large para-spinal abscess

TB Vertebral Osteomyelitis 2 randomized controlled trials (N=331)

– 1964-69 (BMRC), 1975-78 (BMRC-ICMR)

– Pts with thoracic/lumbar disease (T1-S1)– All able to walk at entry– Pts with total bone loss > 3 Units excluded

– chemotx alone (I/PAS18 +/- strep3) vs. chemotx (I/R6) + surgery

• One debridement, one debridement and reconstruction– Follow-up at 1.5, 3, 5, 10 yrs

TB Vertebral Osteomyelitis

Conclusion:– Data insufficient– No statistically significant benefit of routine

surgery

Limitations– Now using better medical and surgical tx

TB Vertebral Osteomyelitis

Outcome ConclusionKyphosis Probably no difference (? Age <15)

Neuro deficit No difference*

Pain Neither trial evaluated pain

Bone fusion No difference

Death, Absence of TB

No difference

Regained activity

No difference

Bone loss No difference

Adverse events 4 deaths due to surgery, 7 bone graft failures

Case 4

Our patient did not have any neurological deficits and did not require surgery

He recovered completely with medical therapy

Thanks!

Jane Carter and Phyllis Losikoff

Case 5

87 yo F from Peru US (1969)

PMH:– HTN– Hyperlipidemia– GERD– H/o BRCA s/p L

mastectomy– R TKR (2006); L TKR

(2007)– h/o LTBI s/p 12 mo INH

Family History: Mother died from TB in 1932 when patient was 10 years old

SH: Travel to Venezuela, Peru. No TB contacts

Case 5

CC: R knee pain worsening over 5 months refractory to medical mgmt and s/p fall

ROS: 30 lb weight loss, fatigue R knee arthrocentesis

• WBC 3780 (92P…), RBC 1260• WBC 6000 RBC 4680

L knee arthrocentesis• WBC 4500 (94P ) RBC 600