TB Infection Control:Principles, Pitfalls, and Priorities

Kevin P. Fennelly, MD, MPHInterim Director

Division of Pulmonary & Critical Care Medicine

Center for Emerging & Re-emerging Pathogens

UMDNJ-New Jersey Medical School

fennelkp@umdnj.edu

Objectives

1. To review basic principles underlying TB transmission and TB Infection Control policies.

2. To review the recent history of TB Infection Control.

3. To discuss personal observations and offer practical solutions to common problems in TB Infection Control.

Is TB an Occupational Disease of HCWs?

Low- & middle-income

countries

High-income countries

LTBI (prevalence)

63% (33-79%) 24% (4-46%)

TB disease(annual incidence)

5.8% (0-11%) 1.1% (0.2-12%)

TB mortality (inpt)(PMR) (outpt)

?? 1.18 (1.04-1.35)

3.04 (1.62-5.19)

- Menzies D et al. IJTLD 2007; 11:593

HCW Deaths due to Nosocomial Transmission of DR-TB

• MDR outbreaks U.S. 1980s-1990s– 9 HCWs died

• All immunocompromised, 8 with HIV– Sepkowitz KA, EID 2005

• XDR-TB outbreak, So Africa, 2006– 52/53 died of unrecognized XDR-TB

• 44/44 tested were HIV+• Median survival from sputa collection=16 days• 2 HCWs died; 4 others sought care elsewhere

– Gandhi N, Lancet 2006

Personal Respiratory Protection Against

M. tuberculosis: Contentious Controversy

Riley experimental TB ward

from Sol Permutt, 2004

Wells-Riley Equation: Mathematical model of airborne

infectionPr{infection}=C/S=1-e(-Iqpt/Q)

WhereC=# S infectedS=# susceptibles exposedI = # infectors (# active pulm TB cases)q = # infectious units

produced/hr/Infectorp = pulm ventilation rate/hr/St = hours of exposureQ = room ventilation rate with fresh air

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

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

Control Measures are Synergistic & Complementary

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

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0.1 1 10 100 1000

Duration of Exposure (hours)

Ris

k o

f M

TB

In

fecti

on

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10

100

1000

Wells-Riley Mathematical Model of Airborne Infection

TB is Spread by Aerosols, NOT sputum

*NOT organism size

Particle size* & suspension in air(* NOT size of bacilli)

• 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

- Courtesy of Sol Permutt, 2004

Six-stage Andersen cascade impactor

Andersen AA. J Bacteriol 1958;76:471.

Cough Aerosol Sampling System

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

Cough-generated aerosols of Mtb:Initial Report from Denver, CO4 of 16 (25%) of SS+ subjects

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

Variability of Infectiousness in TB:Epidemiology

Rotterdam, 1967-69: Only 28% of smear positive patients transmitted infections.

Van Geuns et al. Bull Int Union Tuberc 1975; 50:107

• Case control study 796 U.S. TB cases– Index cases tended to infect most (or all) or

few (or none) of their contacts – Snider DE et al. Am Rev Respir Dis 1985; 132:125

• Ability to publish outbreaks suggests that they are episodic.

Variability of Infectiousness in TB:

Experimental • All infections attributed to 8 of 61 (13%) patients.

50% of infections due to one patient with TB laryngitis.

Riley RL et al. Am Rev Respir Dis 1962; 85:511.

• 3 (4%) of 77 patients produced > 73% of the infections in the guinea pigs.

Sultan L. Am Rev Respir Dis 1967; 95:435.

Recent replication of this model in Peru 118 hospital admissions of 97 HIV-TB coinfected patients 8.5% caused 98% of secondary GP infections 90% due to inadequately treated MDR-TB

Escombe AR et al. PLoS Medicine 2008; 5:e188

Occupational TB in Sub-Saharan Africa

• Malawi– 25% mortality

– Harries AD, Tran R Soc Trop Med Hyg 1999; 93: 32

• Ethiopia• South Africa• Nigeria

– 32 of 2,173 HCWs• 15 (47%) as HIV-TB

– Salami AK, Nigerian J Clin Prac 2008; 11: 32

What is the magnitude and variability of infectious aerosols of M. tuberculosis?

(Can we better identify the most infectious?)

Hypothesis 1: Cough-generated aerosols of Mtb can be measured in resource-limited settings.

Hypothesis 2: Cough-generated aerosols will be detected in approximately 25-30% of patients with PTB.

Cough Aerosol Sampling Systemv.2

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

Relation to Sputum Smear Status31/112 (28%) SS+ subjects

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

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utu

m A

FB

Aerosol Log 10 CFU Sputum AFB

1 2 3 4 5 60

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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

Anatomical deposition: Upper airway -- bronchi -- alveoli

Abstract, ATS International Conference, 2004.

Pitfalls in Administrative Controls• TB Mortality not prioritized or under surveillance (i.e., no data

collection)

• HIV screening of HCWs not prioritized – major risk factor for TB disease & death– HAART now feasible in much of world– HIV screening advocated for adm’t patients in US

• TB laboratory personnel often not involved in TB infection control efforts – Botswana: 1st AFB smear ‘STAT’

• Decisions re: infectiousness falls onto clinicians with variable expertise

Pitfalls in Environmental Controls

• Little or no engineering expertise and support for hospitals & HCFs– No systems of communication / interaction– Different ‘cultures’ and mind-sets

• TB nurses or administrators subject to sales pitches from commercial vendors– UVGI lamps in SANTA facilities– Mobile air filters in Newark, NJ

• Lack of appreciation of natural ventilation…and its limitations!– Low rate of nosocomial infection in Uganda project– High rate in Tugela Ferry

Pitfalls in Personal Respiratory Protection

• Too much attention paid to ‘masks’ at expense of administrative and environmental measures

• Rizdon R et al: Renal unit with poor ventilation

• Inappropriate use on patients

• Focus on fit-testing and regulation rather than on follow up on use in field

• Lack of appreciation that not all respirators provide the same level of protection– Need for more protection in high-risk aerosol-inducing

procedures, e.g., bronchoscopies

TB-IC Practices 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

Summary: TB-IC• Administrative controls most important

component of TB-IC– ‘Suspect and separate!’– Prioritize screening HIV in HCWs

• Prioritize good ventilation in all areas– Back-up in areas with poor ventilation

• Fans, mechanical ventilation, UVGI

• Prioritize personal respiratory protection for high risk settings, esp where admin and environ controls limited