Francesca Torriani, M.D., of UC San Diego Owen Clinicm, presents "Update on International CFAR Grant on Tuberculosis and HIV Screening in Healthcare Workers at Maputo Central Hospital in Mozambique" at AIDS Clinical Rounds

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AIDS CLINICAL ROUNDS

2. UPDATE ON INTERNATIONAL CFAR
GRANT ON TUBERCULOSIS AND HIV
SCREENING IN HEALTHCARE
WORKERS AT MAPUTO CENTRAL
HOSPITAL IN MOZAMBIQUE
Susannah Graves, Elizabete Nunes, Francesca Torriani
AIDS Clinical Rounds
June 13, 2014

3. Background
Source: UNAIDS and WHO 2009 Source: WHO 2010
HIV prevalence:
11.5% in Mozambique
TB incidence rate:
> 300 cases per 100,000

4. Site: Maputo Central Hospital
 1500 beds total
Medicine Wards:
 112+ beds
 >65% patients HIV+
 Pulm TB:
 25-30 cases/mo
 cases in HCW?
 MDR-TB in HCW
 3 cases in 2010
 1 case in 2012
Patients waiting waiting to be seen in the Emergency Room

5. Background & Significance
 Infection control committee chartered Sept 2011
 National TB reference laboratory recently acquired
capacity for mycobacterial culture and DST
 TB control program since 2013
 Unknown prevalence, incidence of HIV and TB in HCW
 Recent study of HCW from Northern Mozambique:
 43% HIV prevalence
 9 new TB cases (2.1% of enrollees).
Casas et al. Tropical Med and International Health. Aug 18, 2011.

6. TB Control Team, MCH

7. Specific Aims
1. To establish the prevalence and incidence
of latent tuberculosis and active tuberculosis
in healthcare workers at Maputo Central
Hospital, Mozambique.
2. To study the operating characteristics of
QFT and TST in diagnosing latent TB in the
healthcare setting in Mozambique.
3. To explore the dose response of
quantitative QFT vs. quantitative TST.

8. Methods
 Study population: Healthcare workers at Maputo General Hospital
 Study Period: 9/15/12 to 4/30/14
 Exclusion criteria:
 Recent active TB
 Immunosuppressive therapy
 <1 year service at MCH
 Questionnaire:
 Contact/ID,
 Demographics
 Symptoms and history of HIV
 TB contacts
 TB symptom Questionnaire
 If no symptoms: PPD
 If symptoms: Induced sputum 2x with AFB smear and culture, GeneXpert
 HIV testing, CD4 count
 Treatment referrals as appropriate for HIV and TB

9. Diagnostic Algorithm for TB
 Questionnaire
 Chest Xray
 Sputum x2 ordered if productive cough
 Pulmonary TB suspect definition
 Symptoms or radiographic evidence of pulmonary disease
 TB Case Definitions – WHO
 Definite: culture positive or 2+ AFB sputum smears
 Smear Negative: 2 NEG smears, abnormal CXR, no response
to a course of broad-spectrum ABX (unless HIV infected)

10. Results

11. Demographics
No TB Active or Latent TB TOTAL OR (IC 95) p
Demographic Characteristics N % N % N %
Total 261 37.8 429 62.2 690
Gender
Male 71 27.2 107 24.9 178 25.8 -
0.564
Female 190 72.8 322 75.1 512 74.2 1.11 (0.78 - 1.57)
Age, years
Median (IQR) 38.3 (31.8 - 49.9) 42.0 (33.0 - 49.0) 41.0 (32.6 - 49.0) 0.051
Mean (SD) 40.4 (10.83) 41.8 (10.12) 41.3 (10.41)
Min - Max 21 67 22 72 21 72
< 30 52 19.9 53 12.4 105 15.2 -
< 0.001
30 - 39 90 34.5 129 30.1 219 31.7 1.41 (0.88 - 2.25)
40 - 49 54 20.7 152 35.4 206 29.9 2.76 (1.66 - 4.59)
50 - + 65 24.9 95 22.1 160 23.2 1.43 (0.87 - 2.36)
Profession
Physician 24 9.2 23 5.4 47 6.8 0.62 (0.31 - 1.25)
0.469
Nurse 47 18.0 75 17.5 122 17.7 1.03 (0.60 - 1.77)
Laboratory Technician 9 3.4 19 4.4 28 4.1 1.36 (0.56 - 3.32)
Auxiliary Personnel 121 46.4 217 50.6 338 49.0 1.16 (0.73 - 1.83)
Administrative Personnel 40 15.3 62 14.5 102 14.8 -
Other 20 7.7 33 7.7 53 7.7 1.06 (0.54 - 2.11)
Educational Level
Elementary or less 50 19.2 119 27.7 169 24.5 -
0.036Middle School 162 62.1 243 56.6 405 58.7 0.63 (0.43 - 0.93)
High School or higher 49 18.8 67 15.6 116 16.8 0.57 (0.35 - 0.95)

12. Clinical Characteristics
No TB Active or Latent TB TOTAL
OR (IC 95) p
Clinical Characteristics N % N % N %
Total 261 429 690
Symptomatic 13 5.0 37 8.6 50 7.2 1.80 (0.94 - 3.46) 0.074
Respiratory Symptoms 11 4.2 34 7.9 45 6.5 1.96 (0.97 - 3.94) 0.056
Other symptoms 5 1.9 13 3.0 18 2.6 1.6 (0.56 - 4.55) 0.373
Contact History
TB Patients 198 75.9 340 79.3 538 78.0 1.22 (0.84 - 1.76) 0.298
Contaminated Products 101 38.7 170 39.6 271 39.3 1.04 (0.76 - 1.43) 0.809
BCG Scar 234 89.7 372 86.7 606 87.8 0.75 (0.46 - 1.23) 0.252
HIV Results Available 245 93.9 400 93.2 645 93.5
Positive 29 11.8 49 12.3 78 12.1 1.29 (0.77 - 2.14) 0.331
Chest Xray Available 236 90.4 399 93.0 635 92.0
With Abnormalities 24 10.2 60 15.0 84 13.2 1.56 (0.94 - 2.59) 0.080

13. HIV Prevalence
 645/690 (93%) were tested for HIV
 78 or 12% tested HIV+
 No differences between TB or no TB infection
 CD4 counts and HIV RNA not available at this time

14. TB infection status and LTBI risk stratification
High-risk LTBI:
• HIV+ with TST ≥ 5mm
• HIV- with TST ≥ 15mm and QFT ≥ 1.0
• 284/425 w LTBI (67%)
Low-risk LTBI:
• HIV+ with TST < 5mm
• HIV- with TST 10-14mm or QFT 0.35-1.0
• 127/425 w LTBI (30%)

15. Positive Predictive Value of TST for QFT+
HIV+ HIV-
PPD+
(mm)
QTF + PPD+
PPD/QFT
Concordance
QTF + PPD+
PPD/QFT
Concordance
5 - 10 2 4 50% - - -
10 - 15 7 8 87% 33 52 63%
≥ 15 14 16 87% 205 249 82%
23 28 82% 238 301 79%
PPV in HIV+ 82.14% (75.07 - 83.83)
PPV in HIV- 79.07% (75.07 - 83.83)
Lower PPD/QFT concordance in groups with lower PPD reactivity
Suggests more cross-reactivity at lower PPD reactivity
Question: In high TB prevalence country, QFT focused low reactors?

16. Risk of TB Acquisition
Multivariate Analysis
Any TB Latent TB, High Risk
Characteristics OR (IC 95) p OR (IC 95) p
Included in model 690 545
Respiratory symptoms 1.83 (0.89 - 3.75) 0.098 2.02 (0.96 - 4.27) 0.064
≥ 10 years of service 1.67 (1.21 - 2.30) 0.002 1.65 (1.16 - 2.34) 0.006
Department
Medicine* (reference) - - - -
OBGYN 1.98 (1.15 - 3.41) 0.014 2.36 (1.31 - 4.26) 0.004
Pediatrics 1.77 (0.99 - 3.17) 0.056 1.71 (0.9 - 3.26) 0.101
Surgery† 4.25 (2.33 - 7.75) < 0.001 3.34 (1.73 - 6.45) < 0.001
Administrative 1.48 (0.71 - 3.08) 0.290 1.01 (0.42 - 2.42) 0.976
Laboratories and Pathology 2.76 (1.42 - 5.38) 0.003 2.49 (1.2 - 5.19) 0.015
Emergency Department 3.36 (1.41 - 7.97) 0.006 2.92 (1.15 - 7.45) 0.024
Other Clinical Services 1.63 (0.92 - 2.91) 0.096 1.66 (0.88 - 3.13) 0.116
Other 1.87 (0.96 - 3.65) 0.065 1.74 (0.83 - 3.65) 0.142
* Medicine includes Dermatology, Gastroenterology, Neurology, Oncology, Cardiology, Psychiatry, Hemodialysis, Pulmonary
† Surgery includes General Surgery, Orthopedics, Operating Room, ENT and Urology

17. Risk of TB by Years of Service
<10 years 10 or more years
0%
20%
40%
60%
80%
100%
With TB infection
(LTBI or active)
without TB infection
OR 1.67; 95% CI 1.21 – 2.30

18. Odds of TB infection by DepartmentMedicine(reference)
Ob/gyn*
Pediatrics
Surgery*
Administration
Laboratories&Pathology*
Emergency&CriticalCare*Otherclinicalservices
Othernon-clinical
0
1
2
3
4
5
6
7
8
9
Reference Department Medicine; 95% CI shown (vertical line) *p<0.05
*
*
*
*
9
8
7
6
5
4
3
2
1
0
OR

19. Conclusions and Next Steps
 Active and latent TB prevalence was as expected high among
HCW at Maputo General Hospital.
 67% of LTBI are high risk, thus meet criteria for LTBI
prophylaxis.
 Workers in several departments are at significantly higher risk
of LTBI, suggesting specific occupational risks.
 The results will be helpful in developing targets for
intervention, including full implementation of FAST
 F-A-S-T: FINDING TB cases ACTIVELY by cough surveillance and rapid
diagnosis, SEPARATION and exposure reduction until effective TREATMENT
starts
 Follow up is planned to evaluate the incidence of LTBI/active
TB and determine the adherence to isoniazid preventive
therapy.

20. What was achieved?
What barriers still exist?
We met goals for:
 Recruitment
 HIV testing and staging
 Diagnostic work up of TB suspects, including sputum
induction
 Maintaning confidentiality
But we still have barriers:
 Adherence with follow-up visits low (only 30%)
 Poor adherence with INH prophylaxis

21. Acknowledgements
 Salma Amade, MD
 Joaquim Aracua, MD
 Orvalho Augusto, MD
 Anilsa Daniel, MD
 Catarina David, MD
 Anila Hassane, MD
 Koen Hulshof, MD
 Philip Lederer, MD
 Kristen Lee, MD
 Anna Levitt, PE
 Elizabete Nunes, MD, PhD
 Susete Peleve, MD
 Francesca Torriani, MD
 Sophia Viegas, MS

22. ID Week, San Francisco, 2013

23. LTBI Screening at UCSD Owen
 Monika Kumaraswamy, MD
 Amy Sitapati, MD
 Davey Smith, MD
 Theodorus Katsivas, MD
 Francesca Torriani, MD
 Presented at ID Week San Francisco 2013

24. QFT Results in HIV Infection
N = 2460
0
500
1000
1500
2000
2500
Positive Negative
NumberofPatients(#)
N= 2236N= 223

25. Positive Quantiferon Results (N = 223)
0
30
60
90
120
Low Positive High Positive
NumberofPatients(#)
QFT 0.36 – 0.99 QFT ≥ 1.0
N= 110 (49%)

26. Very few patients with positive QFT
had CD4 Counts < 200
0
50
100
150
High
Positive
QFT & Low
CD4 Count
(<200)
High
Positive
QFT & High
CD4 Count
(>200)
Low
Positive
QFT & Low
CD4 Count
(<200)
Low
Positive
QFT & High
CD4 Count
(>200)
NumberofPatients(#)
106
5 7
105

27. Patients with positive QFT had better
control of HIV replication
0
0.5
1
1.5
2
2.5
3
3.5
High Positive Low Positive Negative
ViralLoad(log10)
P < 0.005
QFT ≥ 1 QFT ≤ 0.35
P < 0.01
QFT 0.36 – 0.99

28. Discussion
• Our study suggests QFT performance and
degree of positivity may be impaired with
poorly controlled HIV replication and low CD4
cell count.
• Therefore, a positive QFT result, regardless of
the absolute value (low or high) should prompt
clinicians to evaluate for the treatment of LTBI.