1. Tuberculosis in prisons TUBS02
Mass screening for tuberculosis in Brazil’s prisons: Generating a scalable model for early diagnosis and prevention Tuesday 24 July, 14: :00
Julio Croda, PhD, MD

2. Outlines i. Previous studies in Brazilian Prisons
      ii.        Opportunities for Interventions
     iii.        Generating a scalable model for early diagnosis and prevention

3. TB Epidemic in Mato Grosso do Sul Prisoners
Established sentinel site for MoH in Mato Grosso do Sul:
HIV prevalence: 1.6%
20% of new TB cases are in prisoners
Highest incarceration rate in country
Cohort study started in 2013
12 prisons in MS
(8 male and 4 female)
Proportional stratified sample
Case definition:
LTBI: induration ≥ 10 mm in TST
LTBI in HIV: ≥ 5 mm in TST
Active TB: positive smear or culture
We established a sentinel site for Ministry of Health in Mato Grosso do Sul. Mato Groso do Sul has highest incarceration rate and highest proportion of prisoners among new TB cases. Mato Grosso do Sul have a total population of 2 million and half and more than 15% of new TB cases in our of prisoners. We performed a Active surveillence and cohort study in the network of 12 prisons in the 5 biggest cities in the state since 2013 which represent 60% of prisoners in the close system in Mato Grosso do Sul. Mato Grosso do Sul borders of Bolivia and Paraguai and is a route of traffic.
Carbone et al. BMC Infectious Diseases 2015
Sgarbi et al. PlosOne 2015

4. Prospective Cohort Study Results
Baseline LTBI at incarceration: 8%
TST Conversion at 1 year: 272/1060 (25.7%)
Perfect storm of largely susceptible population coming into a high transmission setting
Active TB Incidence: 18/1,412 (1,275 per 100k)

5. Risk Factors for Active TB
Adjusted risk factors associated with active TB is reported productive cough at baseline and drug use over the last year.
Paião et al. BMC Infectious Diseases 2016

6. The individuals per cell in this 3 prisons range from 6 to 13
In general the absolute ventilation is not so bad. But we have a low ventilation when adjusted per person. Overcrowing play a big role in the ventilation.
Urrego J, et al, AJTMH 2015

7. Improving Passive Diagnosis Rates is Insufficient to Control TB
53-70% of prisoners are infected after exposure to a case of TB for 4 months (average between onset of symptoms and diagnosis in these prisons)
Due to mobility, each case of TB has contact (2 weeks) with 37 to 45 inmates in a period of 4 months
Early dx (4 to 3 months) averts only 8% infections
Urrego et al. AJTMH 2015

8. Routine screening for active TB
MoH/WHO recommends screening, yet investment has not been made to implement in prisons
Clear policy-implementation gap
Optimal screening strategies not identified
Cost-effectiveness not performed to guide resource allocation
Challenges in screening prisoners
WHO clinical scores are not effective
~70% of cases are smear- and culture+
Cx performed in 32% of cases nationally
Few of 1,478 prisons have chest x-rays
Research priorities
New technologies for mass screening
Mobile digital chest x-ray and laboratory diagnostic units
The first priority is Routine screening for active TB.
MoH and WHO recommends screening at the entrance and annualy. But until now, this recommendation was not been implement in Brazil and many other countries with high burden of the disease. It’s a clear policy-implementaion gap. And this happen because has not been evaluated the optimal screeing strategy and not performed cost-effectiveness studies to guide resource allocation.
We have some challenge in screening prisoners. WHO clinical scores are not effective. Based your study site, 70% of cases are smear – and culture +, and in the role country only 32% confirmed TB cases performed the culture.
MoH propose to evaluation Xpert in prison to reduced the incidence. But, Juliana Urrego, a master public health student from Yale that went to Brazil, describe that in the prisoners we have 1.6 m2 per inmate, 98% of the cells have worse ventilation than is recommended by WHO, in this conditions 78% of inmates infected by 6 months and decreasing time-to-diagnosis by 25%, 4 to 3 months your data, reduced transmission risk only by 8%. CXR Tends to be more effective, but few of 1,500 prisons have CXRs. In Mato Grosso do Sul state, none of the prison have CXR.
Our research priorities in performed a implementation science study and use mobile digital CXR and laboratory dx units to screening active TB. Based this data, modeling the best combination of exams and timinining of screening to propose future recommendations to MoH and WHO.
Projection of TB incidence under biannual screening with 50% and 70% sensitivity
Milinda, et al. In Preparationw

9. Prospective Mass TB Screening Study: Methods
Three prisons
5,900 prison inmates
Accounts for 75% of all TB cases in the state
Approach
To test all individuals independent of symptoms
Smear, Culture, Xpert
Digital Chest X-Ray to all individuals with automatic reading.
Repeat screening every 6 months for 30 months

10. Methods: Automated Interpretation of X-rays
CAD4TB5 is an automated image interpretation system which scores X-rays for TB risk
Calibrated using the first 80 Xpert+ patients and 200 controls

11. Methods: Automated Interpretation of X-rays
Training data demonstrated high accuracy (AUC 0.88)
Sensitivity and Specificity >80%
Established threshold score for further screening
Identifies high-risk individuals for further screening (sputum testing, clinical evaluation)

12. Preliminary Results: Study Population
Characteristics
Number of Participants (N=5435) %
Age (Mean±SD)
32.4 (9.53)
Race (Black and Mixed)
3,862
71%
Less than 8 year of Schooling
3,571
66%
Report any WHO TB symptoms
2,148
39%
Report productive cough
1,473
27%
Current Smoker
3,159
58%
Drug use over the last year
3,199
59%
Previous incarceration (Median: 3 times)
3,824
70%
Previous TB
523
10%

13. Preliminary Results
Screened 5,435 inmates (November, 2017 – July, 2018)
92% of inmates recruited agreed to participate
Overall, 180 (3.3%) TB cases detected
Xpert+: 160 (2.9%)
Xpert- and Culture+: 10 (0.2%)
Clinical diagnoses: 10 (0.2%)

14. Predictive Value of Cough, WHO Symptom Screen and X-ray Score
Report any WHO TB symptoms
Cough
X-Ray Score ≥ 60
% of TB patients No
<60
6/2593= (0.2%)
≥ 60
19/495 (3.8%)
Yes
4/464 (0.9%)
16/105 (15.2%)
24/1089 (2.2%)
96/348 (27.6%)

15. What may be missed by traditional screening?
TB Cases
(n=180)
No TB
(n=5,255)
Cough < 2 weeks
79 (44%)
4512 (86%)
WHO Symptom Screen Negative
25 (14%)
3262 (62%)
X-Ray Score < 60
34/165* (19%)
4112/4929* (83%)

16. Smoking status and previous TB do not add predictive value over symptom screening and X-ray
Among individuals with cough and abnormal chest x-rays, previous TB did not predict TB (28.7% vs 27.1%, p=0.76)
Inmates who smoke and had cough had no difference in TB risk compared with non-smokers with cough (9.4% vs 6.6%, p=0.07)
These findings indicate that all inmates should be screened for TB by X-ray and symptom screening regardless of TB and smoking history

17. Next Steps Continue screening every six months for next 2 years
Identify cases occurring between screening rounds and missed by mass screening
Determine optimal screening frequency and algorithms to enable efficient and accurate mass screening
New Screening and Prevention Modalities:
Pooling sputum samples
Environmental Screening
Biomarkers to identify subclinical TB or those at risk of progression
INH or BCG revaccination for prevention of infection

18. Funding: NIH (R01 AI130058-01), CNPq and CAPES
This article in the New Times makes it clear that we did not have many innovations regarding to the TB control in prisons since the nineteenth century.
Funding: NIH (R01 AI ), CNPq and CAPES