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

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AIDS CLINICAL ROUNDS

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

Background

Source: UNAIDS and WHO 2009 Source: WHO 2010

HIV prevalence: 11.5% in Mozambique

TB incidence rate: > 300 cases per 100,000

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

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.

TB Control Team, MCH

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.

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

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)

Results

Demographics No TB Active or Latent TB TOTAL OR (IC 95) p

Demographic Characteristics N % N % N %

Total 261 37.8 429 62.2 690 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 -

0.036 Middle 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)

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

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

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%)

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?

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

Risk of TB by Years of Service

<10 years 10 or more years0%

20%

40%

60%

80%

100%

With TB infection (LTBI or active)

without TB infection

OR 1.67; 95% CI 1.21 – 2.30

Odds of TB infection by Department

Medicine (reference)

Ob/gyn*

Pediatrics

Surgery*

Administration

Laboratories & Pathology*Em

ergency & Critical Care*Other clinical services

Other non-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

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.

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

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

ID Week, San Francisco, 2013

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

QFT Results in HIV Infection N = 2460

0

500

1000

1500

2000

2500

Positive Negative

Num

ber

of P

atie

nts

(#)

N= 2236 N= 223

Positive Quantiferon Results (N = 223)

0

30

60

90

120

Low Positive High Positive

Num

ber

of P

atie

nts

(#)

QFT 0.36 – 0.99 QFT ≥ 1.0 N= 110 (49%)

Very few patients with positive QFT had CD4 Counts < 200

0

50

100

150

HighPositive

QFT & LowCD4 Count

(<200)

HighPositive

QFT & HighCD4 Count

(>200)

LowPositive

QFT & LowCD4 Count

(<200)

LowPositive

QFT & HighCD4 Count

(>200)

Num

ber

of P

atie

nts

(#)

106

5 7 105

Patients with positive QFT had better control of HIV replication

00.5

11.5

22.5

33.5

High Positive Low Positive Negative

Vir

al L

oad

(log1

0)

P < 0.005

QFT ≥ 1 QFT ≤ 0.35

P < 0.01

QFT 0.36 – 0.99

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.