The UC San Diego AntiViral Research Center sponsors weekly
presentations by infectious disease clinicians, physicians and
...
UPDATE ON INTERNATIONAL CFAR
GRANT ON TUBERCULOSIS AND HIV
SCREENING IN HEALTHCARE
WORKERS AT MAPUTO CENTRAL
HOSPITAL IN M...
Background
Source: UNAIDS and WHO 2009 Source: WHO 2010
HIV prevalence:
11.5% in Mozambique
TB incidence rate:
> 300 cases...
Site: Maputo Central Hospital
 1500 beds total
Medicine Wards:
 112+ beds
 >65% patients HIV+
 Pulm TB:
 25-30 cases/...
Background & Significance
 Infection control committee chartered Sept 2011
 National TB reference laboratory recently ac...
TB Control Team, MCH
Specific Aims
1. To establish the prevalence and incidence
of latent tuberculosis and active tuberculosis
in healthcare wo...
Methods
 Study population: Healthcare workers at Maputo General Hospital
 Study Period: 9/15/12 to 4/30/14
 Exclusion c...
Diagnostic Algorithm for TB
 Questionnaire
 Chest Xray
 Sputum x2 ordered if productive cough
 Pulmonary TB suspect de...
Results
Demographics
No TB Active or Latent TB TOTAL OR (IC 95) p
Demographic Characteristics N % N % N %
Total 261 37.8 429 62.2 ...
Clinical Characteristics
No TB Active or Latent TB TOTAL
OR (IC 95) p
Clinical Characteristics N % N % N %
Total 261 429 6...
HIV Prevalence
 645/690 (93%) were tested for HIV
 78 or 12% tested HIV+
 No differences between TB or no TB infection
...
TB infection status and LTBI risk stratification
High-risk LTBI:
• HIV+ with TST ≥ 5mm
• HIV- with TST ≥ 15mm and QFT ≥ 1....
Positive Predictive Value of TST for QFT+
HIV+ HIV-
PPD+
(mm)
QTF + PPD+
PPD/QFT
Concordance
QTF + PPD+
PPD/QFT
Concordanc...
Risk of TB Acquisition
Multivariate Analysis
Any TB Latent TB, High Risk
Characteristics OR (IC 95) p OR (IC 95) p
Include...
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)
witho...
Odds of TB infection by DepartmentMedicine(reference)
Ob/gyn*
Pediatrics
Surgery*
Administration
Laboratories&Pathology*
E...
Conclusions and Next Steps
 Active and latent TB prevalence was as expected high among
HCW at Maputo General Hospital.
 ...
What was achieved?
What barriers still exist?
We met goals for:
 Recruitment
 HIV testing and staging
 Diagnostic work ...
Acknowledgements
 Salma Amade, MD
 Joaquim Aracua, MD
 Orvalho Augusto, MD
 Anilsa Daniel, MD
 Catarina David, MD
 A...
ID Week, San Francisco, 2013
LTBI Screening at UCSD Owen
 Monika Kumaraswamy, MD
 Amy Sitapati, MD
 Davey Smith, MD
 Theodorus Katsivas, MD
 Franc...
QFT Results in HIV Infection
N = 2460
0
500
1000
1500
2000
2500
Positive Negative
NumberofPatients(#)
N= 2236N= 223
Positive Quantiferon Results (N = 223)
0
30
60
90
120
Low Positive High Positive
NumberofPatients(#)
QFT 0.36 – 0.99 QFT ≥...
Very few patients with positive QFT
had CD4 Counts < 200
0
50
100
150
High
Positive
QFT & Low
CD4 Count
(<200)
High
Positi...
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 Negati...
Discussion
• Our study suggests QFT performance and
degree of positivity may be impaired with
poorly controlled HIV replic...
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Update on International CFAR Grant on Tuberculosis and HIV Screening in Healthcare Workers at Maputo Central Hospital in Mozambique

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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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Update on International CFAR Grant on Tuberculosis and HIV Screening in Healthcare Workers at Maputo Central Hospital in Mozambique

  1. 1. The UC San Diego AntiViral Research Center sponsors weekly presentations by infectious disease clinicians, physicians and researchers. The goal of these presentations is to provide the most current research, clinical practices and trends in HIV, HBV, HCV, TB and other infectious diseases of global significance. The slides from the AIDS Clinical Rounds presentation that you are about to view are intended for the educational purposes of our audience. They may not be used for other purposes without the presenter’s express permission. AIDS CLINICAL ROUNDS
  2. 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. 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. 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. 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. 6. TB Control Team, MCH
  7. 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. 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. 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. 10. Results
  11. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 22. ID Week, San Francisco, 2013
  23. 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. 24. QFT Results in HIV Infection N = 2460 0 500 1000 1500 2000 2500 Positive Negative NumberofPatients(#) N= 2236N= 223
  25. 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. 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. 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. 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.

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