Transcript Case Presentations - New England TB Consortium

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
5.3
6
12
189
1.0
36
AST: 18
N:61 L:25 M:13 E:0.5 Bas:0.2
ALT: 11
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 cultureconfirmed 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
Cough improved

What would you do?
Sputum smears neg
CXR unchanged
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!
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
–
–

5/09
–
–

6 months tx complete
Rifabutin/I/FQ x 3 mo
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)
2)
3)
4)
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
• 41,168 people who sought
medical advice after recent
travel
Travel time
%
< 1 month
60%
1-6 months
30%
> 6 months
10%
•Risk of latent TB infection
•Short-term: 4/1000
•Long-term: 11/1000
• 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: Demographics
Age (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 pretravel 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)
2)
3)
4)
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
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 backcalculation 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.




Case 4
10.2
13
12.6
383
0.7
36.2
AST: 18
N:85 L:8 M:6.0 E:0 Bas:0
ALT: 14
AP: 66
T. bili: 0.7
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
Conclusion
Kyphosis
Probably no difference (? Age <15)
Neuro deficit
No difference*
Pain
Neither trial evaluated pain
Bone fusion
No difference
Death, Absence No difference
of TB
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