Practical TB Infection Controlfor

Community-based TB Programs

Kevin Fennelly, MD, MPH

Center for Emerging & Re-emerging PathogensInterim Director

Division of Pulmonary & Critical Care MedicineUMDNJ-New Jersey Medical School

fennelkp@umdnj.edu11 June 2008

Objectives• To help identify situations in which there is

an increased risk of TB transmission– people (patients) and places (settings)

• To recommend practical solutions – for programs to help protect staff

• principles and provisions

– for staff • knowledge is power … and prevention !!

Areas I will NOT cover

• Abundant evidence that HCWs are at increased risk for occupational TB infection (and disease)– HCW= anyone exposed to patients

• Risk assessment– Would consider most environments in TB-

endemic countries at high risk

Riley experimental TB ward

from Sol Permutt, 2004

TB is transmitted by aerosols (NOT sputum)

*NOT organism size

Particle size* & suspension in air

• Particle size & deposition site– 100 – 20 – 10 – upper airway– 1 - 5 – alveolar

deposition

• Time to fall the height of a room– 10 sec– 4 min– 17 min– Suspended indefinitely

by room air currents

from Sol Permutt, 2004

Estimates of Mtb Aerosol Production (quanta per hour)

TB ward: pt on Rx

Cavitary TB: no Rx

Laryngeal TB

Bronchoscopy/ETT

Autopsy

1.25

13

60

250

1000

- Fennelly KP. Int J Tuberc Lung Dis 1998; 2: S103

Who is Infectious?

• Sputum smear + > smear –– AFB 3-4+ > AFB 1-2+

• Cavitary > non-cavitary• Close > casual contact• Prolonged > brief contact• Men > women• Young > old

• Borgdorff MW et al. Am J Epidemiol 2001; 154:934

• HIV+ = HIV – • Cruciani M et al. Clin Infect Dis 2001; 33:1922

• MDR vs. DS: ?

Where are Patients Most Infectious?

• Congregate settings– Hospitals– Correctional facilities– Bars– Choirs– Airplanes, ships

• Indoors >> outdoors– Increased with crowding & proximity– But no data on UV-A or UV-B effects

When are Patients Most Infectious?

• Coughing > Singing > Talking• Loudon RG et al. Am Rev Respir Dis 1969;100:165

• Aerosol producing procedures: intubation, bronchoscopy, sputum induction

• Sepkowitz KA. Clin Infect Dis 1996;23:954

• Not on treatment– Unrecognized/undiagnosed– Drug-resistant on standard therapy

H ouseho ld Mem bers w ith P ositive TS Ts by C ough Frequency

0

10

20

30

40

50

Few Moderate Frequent

O v e rnight C ough Fre que ncy

Per

cen

t H

HC

s w

ith

TS

T+

Loudon RG Am Rev Respir Dis 1969, 99: 109.

Cough Frequency & Infectiousness

What is Infectious?

• Dogma: 1-5 micron infectious droplet nuclei (Wells, 1955)– Risk associated with prolonged exposures

• Reality: Wells estimated particle size distribution based on experimental nebulization of bacillary suspensions in lab

– No data from patient-generated aerosols

– Wells calculated droplets less than 25 microns dessicated to size of infectious droplet nuclei in less than one second

Cough Aerosol Sampling System

- Fennelly KP et al. Am J Resp Crit Care Med 2004; 169; 604-9

Six-stage Andersen cascade impactor

Andersen AA. J Bacteriol 1958;76:471.

Cough-generated aerosols of M.tb National Jewish Medical & Research Center

- Fennelly KP et al. Am J Resp Crit Care Med 2004; 169; 604-9

Cough Aerosol Sampling System

Frequency Distribution of Cough-generated Aerosols of M. tuberculosis and

Relation to Sputum Smear Status

0

0.5

1

1.5

2

2.5

3

3.5

1 7 13 19 25 31 37 43 49 55 61 67 73 79 85 91 97 103 109

Subjects Sorted by Aerosol CFU then by Sputum AFB

Aer

oso

l Lo

g C

FU

0

1

2

3

4

5

Sp

utu

m A

FB

Aerosol Log 10 CFU Sputum AFB

1 2 3 4 5 60

10

20

30

40

50

Stage of Andersen Cascade Impactor

Pe

r C

en

t C

FU

Cough-generated Aerosols of M. tuberculosis:

Normalized Particle Sizes

Lower limit of size range(µ) 7.0 4.7 3.3 2.1 1.1 0.65

Deposition Upper airway - bronchi -- alveoli

Abstract, ATS International Conference, 2004.

Cough Aerosol Production:Multivariate Analysis

• Best model in logistic regression– Bacillary concentration: BACTEC™ < 4 days to positive

(OR=11.35, p=0.02) and – strong cough (OR=5.41, p=0.04)

• Cough strength is associated with performance score (physical health) (Chi-square, p=0.004).

– Cough strength tends to be associated with CD4 counts (less advanced HIV infection) (Chi-square, p=0.07).

– CD4 counts and performance scores drop out of multivariate models probably due to correlation with cough strength.

• These data suggest that healthier patients are more likely to be infectious than very ill patients.

0.75 1.00 1.25 1.50 1.75 2.00 2.250

1

2r = 0.77(p<0.001)

Log Aerosol Mtb CFU by Andersen

Lo

g L

un

g C

FU

Da

y 0

Aerosol CFUs Predict Infectivity in Mice

Abstract, Keystone Symposium on Tuberculosis, 2005.

Probability of MTB Infection: Isolation Room with 6 ACH:

Infectiousness and Duration of Exposure

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0.1 1 10 100 1000

Duration of Exposure (hours)

Ris

k o

f M

TB

In

fecti

on

1

10

100

1000

Assumptions: Homogenous distribution of infectious aerosol over 10 hours; uniform susceptibility.

- Fennelly KP & Nardell EA. Infect Control Hosp Epidemiol 1998; 19;754

Wells-Riley Mathematical Model of Airborne Infection

Summary: PrinciplesTB-IC for Community Programs

• The most infectious TB patients are those who are not on appropriate therapy– Undiagnosed, i.e., unrecognized– Drug resistant

• TB is transmitted by aerosols– Coughing and bacillary load important– Healthier patients may be more infectious

• Poorly ventilated indoor environments the highest risk

Summary: PracticesTB-IC for Community Programs

• Best administrative control: – Suspect and separate until diagnosed– Surveillance of HCWs with TST (and/or IGRAs) and rapid

treatment of LTBI if conversions occur

• Best environmental control: Ventilation– Do as much as possible outdoors– Use directional airflow when possible

• Natural breeze or fans: HCW ‘upwind’; patient ‘downwind’

• Personal respiratory protection– N95 respirators when indoors or very close (procedures)– Surgical masks on patients to control source