What’s New in Legionnaires’ Disease? Richard D. Miller, Ph.D. How does it relate to your job? Legionella bacteria

Legionella Live in Water Surface water (lakes, streams, etc) Surface water (lakes, streams, etc) Virtually all have LegionellaVirtually all have Legionella Low numbers - rare diseaseLow numbers - rare disease Actually, Legionella live inside of amoebae and other protozoa that live in the water

Legionella Live in Water Surface water (lakes, streams, etc) Surface water (lakes, streams, etc) Virtually all have LegionellaVirtually all have Legionella Low numbers - rare diseaseLow numbers - rare disease Thermal areas (i.e. near hot springs) Thermal areas (i.e. near hot springs) Elevated numbers – rare diseaseElevated numbers – rare disease

Legionella Live in Water Surface water Surface water Virtually all have LegionellaVirtually all have Legionella Low numbers - rare diseaseLow numbers - rare disease Thermal areas Thermal areas Elevated numbersElevated numbers Rare diseaseRare disease  Building water May have high levels of Legionella May have high levels of Legionella Airborne dissemination Airborne dissemination Legionnaires’ disease Legionnaires’ disease

Hospital- nosocomial LD

Other buildings- community-acquired LD Hotel- travel-associated LD (Europe) EWGLI-NET (37 countries)

Most cases are single isolated events, and the source is never determined

Legionella- are they all equally bad? Large family of at least 50 species (likely >80 species) Large family of at least 50 species (likely >80 species) Do they all cause disease? Do they all cause disease? L. pneumophila – >90% of disease in U.S./Europe L. pneumophila – >90% of disease in U.S./Europe > 14 serogroups (serogroup 1 most common)> 14 serogroups (serogroup 1 most common) Other species- unusual, except in transplant hospitals Other species- unusual, except in transplant hospitals Some guidelines and standards view all Legionella the same and have set limits based on total Legionella New VA Hospital guidelines- Non-transplant hospitals only monitor for L. pneumophila! Thus, unless it is a hospital, ESTech considers the risk for L. pneumophila to be 10-fold greater than with other species. How does this relate to your job?

Legionnaires’ Disease There are still large outbreaks! Most of the estimated 25,000 cases in the U.S. each year are single isolated cases. Most of the estimated 25,000 cases in the U.S. each year are single isolated cases. Multi-case outbreaks still occur each year in the U.S. and the world Multi-case outbreaks still occur each year in the U.S. and the world

Recent Outbreaks- International Netherlands (1999) – flower/home show Jacuzzi Netherlands (1999) – flower/home show Jacuzzi 250 cases, 28 deaths (11%)250 cases, 28 deaths (11%) Melbourne, Australia (2000) – public aquarium cooling tower Melbourne, Australia (2000) – public aquarium cooling tower 113 cases, 2 deaths (2%)113 cases, 2 deaths (2%) Spain (2001, 2006) – cooling towers Spain (2001, 2006) – cooling towers 2001 (Murcia) 449 confirmed case (>600 total), 6 deaths (1%)2001 (Murcia) 449 confirmed case (>600 total), 6 deaths (1%) 2006 (Pamplona) 139 confirmed case, 0 deaths (0%)2006 (Pamplona) 139 confirmed case, 0 deaths (0%) Hiuga City, Japan (2002) – public hot spring bath Hiuga City, Japan (2002) – public hot spring bath 295 cases, 7 deaths (2%)295 cases, 7 deaths (2%) Barrow, UK (2002) – cooling tower Barrow, UK (2002) – cooling tower 179 cases, 7 deaths (4%)179 cases, 7 deaths (4%) Harnes, France (2003) – cooling tower Harnes, France (2003) – cooling tower 86 cases, 18 deaths (21%)86 cases, 18 deaths (21%) Norway (2005) – air scrubber Norway (2005) – air scrubber –55 cases, 10 deaths (18%)

Recent Outbreaks- North America Toronto, Canada (2005) – nursing home, cooling tower Toronto, Canada (2005) – nursing home, cooling tower >110 cases, 20 deaths (patients only) (18%)>110 cases, 20 deaths (patients only) (18%) 71 patients, 23 staff, 14 visitors, 2 neighborhood residents71 patients, 23 staff, 14 visitors, 2 neighborhood residents

Recent Outbreaks- North America Toronto, Canada (2005) – nursing home, cooling tower Toronto, Canada (2005) – nursing home, cooling tower >110 cases, 20 deaths (patients only) (18%)>110 cases, 20 deaths (patients only) (18%) 71 patients, 23 staff, 14, visitors, 2 neighborhood residents71 patients, 23 staff, 14, visitors, 2 neighborhood residents Rapid City, South Dakota (2005) – restaurant, decorative fountain Rapid City, South Dakota (2005) – restaurant, decorative fountain 19 cases, 1 death (5%)19 cases, 1 death (5%) Mayor of Rapid City wasMayor of Rapid City was one of the victims! one of the victims!

Recent Outbreaks- North America Toronto, Canada (2005) – nursing home, cooling tower Toronto, Canada (2005) – nursing home, cooling tower >110 cases, 20 deaths (patients only) (18%)>110 cases, 20 deaths (patients only) (18%) 71 patients, 23 staff, 14, visitors, 2 neighborhood residents71 patients, 23 staff, 14, visitors, 2 neighborhood residents Rapid City, South Dakota (2005) – restaurant, decorative fountain Rapid City, South Dakota (2005) – restaurant, decorative fountain 19 cases, 1 death (5%)19 cases, 1 death (5%) Mayor of Rapid City wasMayor of Rapid City was one of the victims! one of the victims! San Antonio, TX (2006) – hospital, likely cooling tower San Antonio, TX (2006) – hospital, likely cooling tower At least 10 cases, 3 deaths (30%)At least 10 cases, 3 deaths (30%) 5 patients, 5 visitors5 patients, 5 visitors How does this relate to your job? 

Bad publicity for you and your clients

Recent Outbreaks- North America Toronto, Canada (2005) – nursing home, cooling tower Toronto, Canada (2005) – nursing home, cooling tower >110 cases, 20 deaths (patients only) (18%)>110 cases, 20 deaths (patients only) (18%) 71 patients, 23 staff, 14 visitors, 2 neighborhood residents71 patients, 23 staff, 14 visitors, 2 neighborhood residents $600 million class action lawsuit! Bad financially for you and your clients

Outbreak in cases, 1 death 2006, Federal jury verdict- $193 million against Essef Corp (spa filter manufacturer) awarded to Celebrity Cruise.

Outbreak in cases, 1 death 2007, Federal District Court overturned all but $10 million of the award

Gillian Beckingham Architect Head of Design Services for the Barrow Borough Council Britain’s Worst LD Outbreak Barrow Arts Center cases (perhaps 500 more), 7 deaths Tried on 7 counts of manslaughter for failing to have a contract for treating the Arts Centre cooling tower Tried on 7 counts of manslaughter for failing to have a contract for treating the Arts Centre cooling tower Acquitted by a jury, but fined £15,000 for breach of health and safety laws Acquitted by a jury, but fined £15,000 for breach of health and safety laws Barrow Borough Council was fined £125,000 Barrow Borough Council was fined £125,000

Gillian Beckingham Architect Head of Design Services for the Barrow Borough Council Britain’s Worst LD Outbreak Barrow Arts Center cases (perhaps 500 more), 7 deaths Tried on 7 counts of manslaughter for failing to have a contract for treating the Arts Centre cooling tower Tried on 7 counts of manslaughter for failing to have a contract for treating the Arts Centre cooling tower Acquitted by a jury, but fined £15,000 for breach of health and safety laws Acquitted by a jury, but fined £15,000 for breach of health and safety laws Barrow Borough Council was fined £125,000 Barrow Borough Council was fined £125,000 This can be prevented!

Legionnaires Disease Prevention Legionella Guidelines Legionella Guidelines VHA - Prevention of Legionella Disease, 2008VHA - Prevention of Legionella Disease, 2008 WHO - Legionella and the Prevention of Legionellosis, 2007WHO - Legionella and the Prevention of Legionellosis, 2007 CDC - Guideline for Prevention of Nosocomial Pneumonia, 2003CDC - Guideline for Prevention of Nosocomial Pneumonia, HICPAC Guideline for Environmental Infection Control in Healthcare Facilities, HICPAC Guideline for Environmental Infection Control in Healthcare Facilities, 2001 State of Maryland (hospitals), other statesState of Maryland (hospitals), other states Pittsburgh / Allegheny County (hospitals)Pittsburgh / Allegheny County (hospitals) Professional OrganizationsProfessional Organizations  ASHRAE (American Society of Heating, Refrigerating, and Air-Conditioning Engineers) Air-Conditioning Engineers)  AWT (Association of Water Technologies)  CTI (Cooling Technology Institute)

Legionnaires Disease Prevention Legionella Guidelines Legionella Guidelines Problems Problems  No widespread implementation of any of these guidelines  No agreement on what to do, including whether to monitor for Legionella and how to interpret the results.

Legionnaires Disease Prevention Defined process with specific steps Defined process with specific steps Similar to HACCP that has been successful in the food industry Similar to HACCP that has been successful in the food industry Hazard Analysis Critical Control PointHazard Analysis Critical Control Point  Framework for the new WHO document (2007) “Legionella and Prevention of Legionellosis” What’s new? Legionella Risk Management

Legionnaires Disease Prevention Defined process with specific steps Defined process with specific steps Similar to HACCP that has been successful in the food industry Similar to HACCP that has been successful in the food industry Hazard Analysis Critical Control PointHazard Analysis Critical Control Point  Framework for the new WHO document (2007) “Legionella and Prevention of Legionellosis” and the new ASHRAE Standard (in preparation) What’s new? Legionella Risk Management

Legionnaires Disease Prevention Defined process with specific steps Defined process with specific steps Similar to HACCP that has been successful in the food industry Similar to HACCP that has been successful in the food industry Hazard Analysis Critical Control PointHazard Analysis Critical Control Point  Format for the new WHO document (2007) “Legionella and Prevention of Legionellosis” and the new ASHRAE Standard (in preparation) What’s new? Legionella Risk Management

Legionnaires Disease Prevention Identify all uses for and occurrences of water at a facility and prepare process flow diagrams Identify all uses for and occurrences of water at a facility and prepare process flow diagrams Conduct a hazard analysis (i.e. Legionella) Conduct a hazard analysis (i.e. Legionella) Identify critical control points in the process to eliminate or control the hazard and implement the controls Identify critical control points in the process to eliminate or control the hazard and implement the controls Describe the critical limits for the hazard Describe the critical limits for the hazard Establish a monitoring plan to validate the control measures Establish a monitoring plan to validate the control measures Legionella Risk Management

Legionnaires Disease Prevention Identify all uses for and occurrences of water at a facility and prepare process flow diagrams Identify all uses for and occurrences of water at a facility and prepare process flow diagrams Conduct a hazard analysis (i.e. Legionella) Conduct a hazard analysis (i.e. Legionella) Legionella Risk Management

Building Water Use Assessment – Legionella Hazard  Cooling towers and evaporative condensers

Recent Outbreaks- International Netherlands (1999) – flower/home show Jacuzzi Netherlands (1999) – flower/home show Jacuzzi 250 cases, 28 deaths (11%)250 cases, 28 deaths (11%) Melbourne, Australia (2000) – public aquarium cooling tower Melbourne, Australia (2000) – public aquarium cooling tower 113 cases, 2 deaths (2%)113 cases, 2 deaths (2%) Murcia, Spain (2001) – cooling tower Murcia, Spain (2001) – cooling tower 449 confirmed case (>600 total), 6 deaths (1%)449 confirmed case (>600 total), 6 deaths (1%) Hiuga City, Japan (2002) – public hot spring bath Hiuga City, Japan (2002) – public hot spring bath 295 cases, 7 deaths (2%)295 cases, 7 deaths (2%) Barrow, UK (2002) – cooling tower Barrow, UK (2002) – cooling tower 179 cases, 7 deaths (4%)179 cases, 7 deaths (4%) Harnes, France (2003) – cooling tower Harnes, France (2003) – cooling tower 86 cases, 18 deaths (21%)86 cases, 18 deaths (21%) Norway (2005) – air scrubber Norway (2005) – air scrubber –55 cases, 10 deaths (18%)

Recent Outbreaks- North America Toronto, Canada (2005) – nursing home, cooling tower Toronto, Canada (2005) – nursing home, cooling tower >110 cases, 20 deaths (patients only) (18%)>110 cases, 20 deaths (patients only) (18%) 71 patients, 23 staff, 14 visitors, 2 neighborhood residents71 patients, 23 staff, 14 visitors, 2 neighborhood residents Already a $600 million class action law suit against the nursing homeAlready a $600 million class action law suit against the nursing home

Lidköping, Sweden Community-acquired vs nosocomial disease Community-acquired vs nosocomial disease Community-acquired disease Community-acquired disease Point source epidemics – cooling towers, JacuzzisPoint source epidemics – cooling towers, Jacuzzis Inhalation of infectious aerosolsInhalation of infectious aerosols People have been infected as far as 6 miles from the source!!People have been infected as far as 6 miles from the source!! Very large numbers of Legionella in the contaminated waterVery large numbers of Legionella in the contaminated water 32 cases from industrial cooling tower 1 km from town Unusual wind direction

Building Water Use Assessment – Legionella Hazard Hot tubs and Jacuzzis Hot tubs and Jacuzzis

Building Water Use Assessment – Legionella Hazard Hot tubs and Jacuzzis Hot tubs and Jacuzzis 50 cases, 1 death

Recent Outbreaks- International Netherlands (1999) – flower/home show Jacuzzi Netherlands (1999) – flower/home show Jacuzzi 250 cases, 28 deaths (11%)250 cases, 28 deaths (11%) Melbourne, Australia (2000) – public aquarium cooling tower Melbourne, Australia (2000) – public aquarium cooling tower 113 cases, 2 deaths (2%)113 cases, 2 deaths (2%) Murcia, Spain (2001) – cooling tower Murcia, Spain (2001) – cooling tower 449 confirmed case (>600 total), 6 deaths (1%)449 confirmed case (>600 total), 6 deaths (1%) Hiuga City, Japan (2002) – public hot spring bath Hiuga City, Japan (2002) – public hot spring bath 295 cases, 7 deaths (2%)295 cases, 7 deaths (2%) Barrow, UK (2002) – cooling tower Barrow, UK (2002) – cooling tower 179 cases, 7 deaths (4%)179 cases, 7 deaths (4%) Harnes, France (2003) – cooling tower Harnes, France (2003) – cooling tower 86 cases, 18 deaths (21%)86 cases, 18 deaths (21%) Norway (2005) – air scrubber Norway (2005) – air scrubber –55 cases, 10 deaths (18%)

Building Water Use Assessment – Legionella Hazard Potable water (hot water tanks, faucets) Potable water (hot water tanks, faucets) The most prominent source in hospital patients Chronic colonization of the potable water system Buildings with hot water temperature less than 124° F (51° C )

Building Water Use Assessment – Legionella Hazard Cooling towers and evaporative condensers Cooling towers and evaporative condensers Potable water (hot water tanks, faucets, showers) Potable water (hot water tanks, faucets, showers) Hot tubs and Jacuzzis Hot tubs and Jacuzzis Indoor decorative fountains Indoor decorative fountains Humidifiers, mister systems Humidifiers, mister systems Industrial process water Industrial process water

Legionnaires Disease Prevention Identify all uses for and occurrences of water at a facility and prepare process flow diagrams Identify all uses for and occurrences of water at a facility and prepare process flow diagrams Conduct a hazard analysis (i.e. Legionella) Conduct a hazard analysis (i.e. Legionella) Identify critical control points in the process to eliminate or control the hazard and implement the controls Identify critical control points in the process to eliminate or control the hazard and implement the controls Legionella Risk Management Cooling Towers - Biocide Use Which biocides work best against Legionella?

Cooling Tower Biocide Study Published in ASHRAE Transactions in ,590 water samples were collected by chemical treatment personnel from ~1,000 different cooling towers throughout the U.S. (primarily eastern U.S.) 2,590 water samples were collected by chemical treatment personnel from ~1,000 different cooling towers throughout the U.S. (primarily eastern U.S.) Samples were to be collected prior to any slug dosing of biocides (biocide control at its lowest) Samples were to be collected prior to any slug dosing of biocides (biocide control at its lowest) Samples were shipped overnight to our lab for analysis: Legionella culture (limit of sensitivity was 10 cfu/ml) Samples were shipped overnight to our lab for analysis: Legionella culture (limit of sensitivity was 10 cfu/ml) Specific biocides, concentration and dosage schedule were chosen entirely by chemical treatment representatives as part of their normal maintenance. Specific biocides, concentration and dosage schedule were chosen entirely by chemical treatment representatives as part of their normal maintenance.

Cooling Tower Biocides 8 different biocides alone or in combination 28 different combinations Non-Oxidizing biocides Non-Oxidizing biocides QuatQuat CarbamateCarbamate IsothiazolinoneIsothiazolinone Brominated nitrilopropionamide (DBNPA)Brominated nitrilopropionamide (DBNPA) GlutaraldehydeGlutaraldehyde Tetrakis(hydroxymethyl)phosphonium sulfate (THPS)Tetrakis(hydroxymethyl)phosphonium sulfate (THPS)  Oxidizing biocides Sodium bromide + trichlorisocyanuric acidSodium bromide + trichlorisocyanuric acid HydroperoxideHydroperoxide

Data Analysis Each of the 28 treatments compared to the overall prevalence in all of the towers (n=2,590): Each of the 28 treatments compared to the overall prevalence in all of the towers (n=2,590): Legionella prevalence (>10/ml)- 13% (±1) Legionella prevalence (>10/ml)- 13% (±1) High Legionella (>1,000/ml) prevalence- 2% (±1) High Legionella (>1,000/ml) prevalence- 2% (±1) Question- Which biocide combinations were statistically better or worse than average?

Prevalence of Legionella in Towers with: Bromine (n=572) Legionella (%±CI) High Legionella (%±CI) Legionella (%±CI) High Legionella (%±CI) Bromine alone 30/130 (23 ±7 ) 6/130 (5 ±3 ) + quat 5/135 (4 ±3 ) 1/135 ( 1 ±4 ) + carbamate 4/36 (11 ±8 ) 1/36 ( 3 ±12 ) + isothiazolinone 21/128 ( 16 ±6 ) 3/128 ( 2 ±5 ) + glutaraldehyde 21/103 ( 20 ±7 ) 7/103 ( 7 ±4 ) + DBNPA 8/19 (42 ±22 ) 0/19 ( 0 ±18 ) + THPS 0/21 ( 0 ±16 ) 0/21 ( 0 ±16 ) Total bromine 89/572 (16±3) 18/572 (3±1) Overall average 626/2590 (13±1) 106/2590 (2±1)

Summary General Conclusions Many different biocide combinations worked well to control Legionella colonization. Many different biocide combinations worked well to control Legionella colonization. There was no magic bullet. None of the biocide combinations was always effective in preventing Legionella colonization and none always failed. There was no magic bullet. None of the biocide combinations was always effective in preventing Legionella colonization and none always failed. Combinations of two non-oxidizing biocides were usually just as good, and frequently better, than an oxidizing/non-oxidizing combination. Combinations of two non-oxidizing biocides were usually just as good, and frequently better, than an oxidizing/non-oxidizing combination.

Summary Legionella-Biocide Trends THPS- significantly more effective than most of the other biocide combinations tested. THPS- significantly more effective than most of the other biocide combinations tested. Bromine- combinations with Quats and THPS were better than average, but other combos trended toward more prevalent Legionella. Bromine- combinations with Quats and THPS were better than average, but other combos trended toward more prevalent Legionella. Quats- as effective as other biocides in most combinations (contrary to popular opinion). The quat/bromine was better than average. Quats- as effective as other biocides in most combinations (contrary to popular opinion). The quat/bromine was better than average. DBNPA- statistically worse than the other non-oxidizing biocides DBNPA- statistically worse than the other non-oxidizing biocides Please keep sending biocide information!!

New Biocide Data

Legionnaires Disease Prevention Identify all uses for and occurrences of water at a facility and prepare process flow diagrams Identify all uses for and occurrences of water at a facility and prepare process flow diagrams Conduct a hazard analysis (i.e. Legionella) Conduct a hazard analysis (i.e. Legionella) Identify critical control points in the process to eliminate or control the hazard and implement the controls Identify critical control points in the process to eliminate or control the hazard and implement the controls Legionella Risk Management Cooling Towers – Drift eliminators Theoretical implications – what is the infectious particle?

Tests show that most of the volume of drift is contained in ≤100 μ droplets Assume all drift were in 100 μ dia water spheres with the volume of each drop = 0.5 x 10 6 cubic μ, then each ml of drift would contain 2 x 10 6 droplets of water. In a typical CT there is a pound of air passing through the tower for each pound of water. A 1000-ton CT will circulate 3000 gpm of water with Evapco’s counterflow towers generate 0.03 gpm of drift (113 ml). This drift would be contained in 350,000 CFM of air. Concentration of Legionella in Cooling Tower Exhaust (Drift)?

If there are 100 Legionella/ml, then each minute 11,3000 Legionella bacteria are dispersed in 350,000 cu ft of air or about 1 Legionella per 30 cu ft or 850 liters Typical adult takes breaths per min of 500 ml volume. Thus, if one inhaled only undiluted drift, an average person would inhale less than a single Legionella per hour! Concentration of Legionella in Cooling Tower Exhaust (Drift)?

For outbreaks to occur, Legionella must be dispersed as packets: Explanation?  Poor drift eliminators leading to large droplets released (containing multiple Legionella) evaporated to a small micron dia droplet

For outbreaks to occur, Legionella must be dispersed as packets: Explanation?  Poor drift eliminators leading to large droplets released (containing multiple Legionella) evaporated to a small micron dia droplet  Pieces of biofilm break off (must be small to get in lungs)  Packets of packaged Legionella from protozoa

Legionella pellets expelled from the ciliate Tetrahymena

Legionnaires Disease Prevention Identify all uses for and occurrences of water at a facility and prepare process flow diagrams Identify all uses for and occurrences of water at a facility and prepare process flow diagrams Conduct a hazard analysis (i.e. Legionella) Conduct a hazard analysis (i.e. Legionella) Identify critical control points in the process to eliminate or control the hazard and implement the controls Identify critical control points in the process to eliminate or control the hazard and implement the controls Describe the critical limits for the hazard Describe the critical limits for the hazard Establish a monitoring plan to validate the control measures Establish a monitoring plan to validate the control measures Legionella Risk Management

Legionnaires Disease Prevention Total bacterial counts are not a substitute for Legionella monitoring (except for perhaps in whirlpool spas). Total bacterial counts are not a substitute for Legionella monitoring (except for perhaps in whirlpool spas). Viable Legionella tests are still the accepted “Gold Standard” for monitoring. Viable Legionella tests are still the accepted “Gold Standard” for monitoring. Tests based on nucleic acid (PCR) or antigen detection are useful in emergency situations and positive tests need to be confirmed with culture Tests based on nucleic acid (PCR) or antigen detection are useful in emergency situations and positive tests need to be confirmed with culture Validation- Legionella Monitoring What’s new in Legionella monitoring?

Thank you Questions?