New

perspectives

in outbreak

investigation

and exposure

management

Susan M. Kellie, MD,

MPH

Professor Emerita,

University of New

Mexico SOM

Division of

Infectious Diseases

Objectives: learn how to….

• Follow the steps in outbreak investigation-but know when to jump ahead!

• Follow the steps in exposure management

• Place outbreak investigation and exposure management within the overall incident management framework

• Communicate with public health and federal agencies for patient safety

The role of the IP/HE• Establish that an outbreak is occurring

• Create a case definition

• Find out the who, what, when, where and how of each case

• Examine all records to find unrecognized cases

• Make a tentative hypothesis

• Implement an intervention

• Refine the case definition and re-examine the hypothesis as new information is gathered

• Test the hypothesis using case-control or other statistical methods

Define the outbreak • Outbreak epidemiology is the study of a disease

cluster or epidemic in order to control or prevent further spread of disease in a population.

• Outbreaks are defined by context• Community-based

• Social networks

• School-based

• Healthcare-associated

• Institution-based • Prisons

• Armed forces

• LTCFs

• International

Defining the scope of the outbreak • Defined by scale, time course and relative

numbers:

• Outbreak• Can be one case of an unusual pathogen

• Epidemic• Widespread in a population

• Pandemic• Worldwide

Theme 1: your case may indicate a wide-spread issue

• Lyman et al. Invasive Nontuberculous Mycobacterial Infections among Cardiothoracic Surgical Patients Exposed to Heater–Cooler Devices. Emerg Infect Dis. 2017;23(5):796-805.

Biofilm visualized on surfaces submerged in an internal water reservoir of a heater–cooler device during investigation of invasive extrapulmonary nontuberculous mycobacteria infections among patients who underwent cardiothoracic surgery, York, Pennsylvania, USA, 2015.

Looking for cases: • In July 2015, the Pennsylvania

Department of Health notified the Centers for Disease Control and Prevention (CDC) about a cluster of NTM infections among cardiothoracic surgical patients at 1 hospital. This investigation confirmed a large US outbreak of invasive MAC infections in a previously unaffected patient population and suggested transmission occurred by aerosolization from HCDs.

Molecular strain typing by pulsed-field gel electrophoresis of case-patients and environmental isolates of Mycobacterium chimaera

But the bloodhound smells something else!

An international outbreak is also a point-source outbreak

• Whole genome sequencing was completed on isolates from 11 patients and from five Stöckert3T heater-cooler devices from hospitals in Pennsylvania and Iowa.

• Results revealed a maximum of 38 SNPs between any two isolates related to the outbreak investigation.

• These results strongly suggest a point-source contamination of Stöckert 3T heater-cooler devices.

The outbreak was international• Preliminary typing results of M.

chimaera from heater-cooler devices from three different European countries were almost identical to samples obtained from the manufacturing site.

• Over 250,000 procedures using cardiopulmonary bypass are performed in the United States each year. Stöckert 3T heater-cooler devices represent approximately 60% of the U.S. market

• CDC. MMWR. Notes from the Field: Mycobacterium chimaera Contamination of Heater-Cooler Devices Used in Cardiac Surgery — United States October 14, 2016 / 65(40);1117–1118

Corollary themes from this outbreak: • Microbiology is difficult: A sequencing-based

method is currently the only method that can discriminate between M. chimaera and M. intracellulare.

• The device may not be able to be immediately removed or replaced

• Symptoms and signs of infection can be subtle and patient notification and risk communication can be challenging.

"A wild-eyed

and frantic

young man

burst into

the room”

The Adventure

of the

Norwood

Builder

Recognizing the outbreak • Requires an ongoing surveillance system

focused on the disease in question

• OR

• An entity to which clinicians or others may report suspected cases• Requires an astute clinician in the field to

recognize and report, and awareness of the professional and legal reporting obligation.

Statutory surveillance-sometimes one case is enough

Florida, 2001• In the early morning of

October 2, 2001, a confused and febrile patient walked into the emergency department of a Florida hospital.

• Responding to a request for a “stat” ID consult, Dr. Bush examined a by-then comatose man, interviewed his wife standing at the bedside, and hastened to the laboratory to inspect a Gram-stained sample of his cerebrospinal fluid.

• Bush LM, Perez MT. The Anthrax Attacks 10 Years Later. Annals of Internal Medicine, October 2011 (online at annals.org)

Fortune favors the prepared mind: core reading

• Berton Roueche, The Medical Detectives

• Morbidity and Mortality Weekly Report: free electronic subscription at http://www.cdc.gov/mmwr/mmwrsubscribe.html

• ProMed-useful during pandemic, run by International Society for Infectious Diseases

• http://www.promedmail.org/aboutus/

• Emerging Infectious Diseases- free online or print journal from CDC

“There are known knowns. These are things we know that we know. There are known unknowns. That is to say, there are things that we know we don't know. But there are also unknown unknowns. There are things we don't know we don't know.”

Donald Rumsfeld

WHO List of priorities for R&D• Crimean-Congo haemorrhagic fever (CCHF)• Ebola virus disease and Marburg virus disease• Lassa fever• MERS and SARS• Nipah and henipaviral diseases• Rift Valley fever (RVF)• Zika• Disease X-Disease X represents the knowledge that a

serious international epidemic could be caused by a pathogen currently unknown to cause human disease, and so the R&D Blueprint explicitly seeks to enable cross-cutting R&D preparedness that is also relevant for an unknown “Disease X” as far as possible.

• http://www.who.int/blueprint/priority-diseases/en/

Bacillus pseudobacteremiaoutbreak, UNMHSC summer 2010

• In June of 2010, epidemiology was notified by ID of an unusual number of blood cultures growing Bacillus species. Alert clinician!

• Rapid chart review of the first few patients showed that the patients were probably not infected and this was probably a pseudo-outbreak or outbreak of pseudobacteremias.

Initial steps

• Bacillus is an ubiquitous spore-forming organism able to survive for months to years on environmental surfaces

• Review of prior Bacillus outbreaks indicated that they were often associated with construction, and were more frequent in the summer for unknown reasons.

• A prospective surveillance system was initiated.

Next steps• Develop a case definition

• May be syndromic only• May be pathogen-based

• Find as many cases retrospectively and prospectively as possible. • The index patient (first reported) may not be the first patient• Communicate with your data sources-EDs, labs, pathologists,

office-based clinicians.

• Have lab hold all specimens submitted from source patients or those potentially at risk.

• Secure samples of the suspected vehicle• Review all records to establish a baseline rate

and confirm the existence of an outbreak

The line listing

• Epidemiology’s low-tech tool:

• List of cases with • Demographic details and contact information

• All pertinent details of who what when where and how

• Isolates and other test results.

• Relationship to others in the line listing

• Flexible, expandable, and scannable (by the naked eye).

Field investigation: aka Shoe-leather epidemiology

• “On proceeding to the spot, I found that nearly all the deaths had taken place within a short distance of the [Broad Street] pump. There were only ten deaths in houses situated decidedly nearer to another street-pump. In five of these cases the families of the deceased persons informed me that they always sent to the pump in Broad Street, as they preferred the water to that of the pumps which were nearer. In three other cases, the deceased were children who went to school near the pump in Broad Street...”

• —John Snow, letter to the editor of the Medical Times and Gazette

Field investigation

• May include:• Contents of the fridge• Environmental sampling• Animal trapping• Observations of practices in healthcare• Testing of potentially exposed individuals to find

asymptomatic carriage or past infection• In-depth interviews to determine occupational or

social exposures. • Tracking distribution networks of drugs, food, or

other potential vehicles.

"You consider that to be important?" he

[Inspector Gregory] asked.

"Exceedingly so.”

"Is there any point to which you would wish

to draw my attention?”

"To the curious incident of the dog in the

night-time.”

"The dog did nothing in the night-time.”

"That was the curious incident," remarked

Sherlock Holmes.

Analysis of laboratory processes• The lab, Tricore, also performed cultures for

Presbyterian hospital, where there had been no reported increase in Bacillus isolates.

• The blood culture bottles came from different lots.• Environmental cultures of the lab and incubator did

not reveal any Bacillus isolates.• Inspection of the blood culture bottle storage area in

the satellite lab did not show any gross dust or contamination.

• The blood cultures were often sent via the hospital tube system after draw to the satellite lab for transport to Tricore.

• At this point, it seemed likely that the blood culture bottles were being contaminated at the point of use.

"Look at

that with

your

magnifying

glass,

Mr. Holmes”

The

Adventure

of the

Norwood

Builder

Observations:

• Most of the blood cultures were drawn in the ED

• Tour of ED showed gross dust in the lab room, covering bottles, and other dust in storage areas

• Ambulance bay automatic doors often open

• Most blood cultures were drawn using the technique of drawing all labs from the newly placed IV –observed in person by an IP

Talking to Those involved

at the site of the outbreak

Preliminary actions

• Cleaning in ED

• Attempt to convert ED personnel to best practices for blood cultures

• Outbreak continued

• All medications given to patients were reviewed to make sure there were no commonalities.

• Patients were all reviewed for site of culture, outcome and therapy.

More investigations: • Some cultures had been drawn on 3E, oncology

ward

• Walk-through on 3E showed that construction of 3N was in progress

• A non-functioning fire door had been propped open

• A strong draft was felt from the construction area towards 3E

• Large amounts of dust and debris were in the connecting corridor-dust bunny photo sent to admin!

• Laundry cart in 3E showed dust on packages of sheets.

Blood culture results period May-Oct 2010All blood cultures ED other

Bacillus 43 34

All cultures 2531 6438

totals 2574 6472

OR of Bacillus being isolated from blood cultures drawn in ED vselsewhere= 3.22 (95% CI 2.05-5.06, p<0.001)

Conclusion: Blood cultures growing Bacillus species were significantly more likely to be from the Emergency Room than elsewhere in the hospital in the period from May-Dec 2010.

Controlling for ED contamination

• In order to control for the overall rate of contamination in the ED (4.4%), as opposed to elsewhere in the hospital (2.1%), the proportion of Bacillus among all contaminants was compared for the blood cultures drawn in the ED to blood cultures drawn elsewhere. The odds ratio of Bacillus species being a contaminant in blood cultures drawn in the ED as opposed to elsewhere in the hospital was 1.67 (95% CI 0.97-2.84, p=0.06).

Was the higher rate of Bacillus contamination in the ED related to location itself or a higher rate of overall contamination in the ED?

Contaminated blood cultures only

ED Non-ED

Bacillus 43 34

Other contaminants 79 104

OR=1.67 (95% CI 0.97-2.84), p=0.06

"Holmes opened

it and smelled

the single cigar

which

it contained”

The Adventure

of the Resident

Patient

Construction site of the new Lomas garage, summer 2010

Constructing the epidemic curve

• Frequency histogram

• The overall shape of the epidemic curve can reveal the type of outbreak• Common source with prolonged exposure

• May reveal seasonal variation

• Point source (common source with short exposure)

• Propagated-days between peaks approximate the incubation period

The epidemic curve

0

5

10

15

20

25

30

Jan Feb March April May June July August Sept Oct Nov Dec

Bacillus sp in UH Blood Cultures 2008- Jan 31 2011

2008200920102011

Theme 2: coordinating observations and all available technological and epidemiologic tools is critical

"You have formed a theory, then?"

"At least I have got a grip of the essential facts of the case. I shall

enumerate them to you, for nothing clears up a case so much as

stating it to another person, and I can hardly expect your co-

operation if I do not show you the position from which we start."

I lay back against the cushions, puffing at my cigar, while Holmes,

leaning forward, with his long, thin forefinger checking off the

points upon the palm of his left hand, gave me a sketch of the

events which had led to our journey.

What is this “Disease X”?

Immediate steps after suspecting presence of an outbreak

• Contact authorities-facility, local, state, federal, as appropriate

• Confirm the outbreak and begin the investigation

• Review existing information

• Literature review on similar outbreaks, understand the nature of the pathogen• Know transmission, syndromes caused, incubation

period, likely vehicles, conditions fostering growth, etc

Immediate interventions in management of varicella exposure in a NICU-alerting

• Confirm diagnosis of varicella in the index case.

• Notify Department of Health.

• Notify leadership and convene multidisciplinary action team.

Prepare essential information to present to the working group

• Define exposure interval and determine exposed cohort of patients and health care workers.

• Review facility engineering records of airflow to aid exposure assessment.

• Determine dates and timeline for implementing interventions based on exposure and incubation periods.

Banach et al. Outbreak Response and Incident Management: SHEA Guidance and Resources for Healthcare Epidemiologists in United States Acute-Care Hospitals. ICHE Dec 2017, vol. 38, no. 12

Plans should be flexible and scalable

1. Within the category of biologic events, such as influenza pandemics or outbreaks of emerging pathogens, the EOP leverages commonalities between microorganisms (eg, mode of transmission, laboratory risk, waste management needs).

2. Protocols for coordinating with external entities

3. Personnel training

Rapid actions: do time-limited interventions • Administer prophylactic therapy to neonates,

to include immune globulin and acyclovir as indicated.

• Notify parents of exposed and discharged patients and recall any exposed and discharged neonates for therapy as indicated.

• Identify essential personnel.

Take care of your workforce

• Assess health care worker immunity by review of records, with serologic testing as indicated.

• Notify laboratory if large numbers of personnel require serologic testing.

• Contact pharmacy to ensure an adequate supply of varicella vaccine.

Things to do after day 1-2: intensive ongoing communication • Develop and disseminate a timeline with

dates for interventions such as isolation of the exposed cohort and dates of furlough, etc.

• Communicate with critical services, such as obstetrics, maternal-fetal medicine consultants, pediatrics, and pediatric subspecialities.

• Notify parents and volunteers.

Continuous assurance to prevent new cases and new exposures

• Restrict visitation and offer parents assessment for varicella immunity and immunization as needed.

• Develop a means of identifying those persons cleared to enter the unit.

Next actions: coordinate with other groups-facilities, clinicians• Prepare to sequester the exposed cohort of

neonates and close the unit to new admissions.• Stratify the neonates by risk of exposure and

use available negative air-flow rooms for those at highest risk.

• Coordinate employee reassignments with other units, Human Resources, departments, and Graduate Medical Education.

• Disseminate information to clinicians on recognition and treatment of varicella in the neonate.

Lessons learned: • Serologic assessment: The latex agglutination

assay may yield false positive tests for varicella. We required all personnel to undergo serologic testing by enzyme-linked immunosorbent assay (ELISA) if their last serology was before 2004, the year that latex agglutination testing was no longer marketed

• “Isolettes” don’t isolate

• Traffic of employees into NICU was large and diverse• Susan M. Kellie, MD, MPH, Monear Makvandi, MPH, and

Martha L. Muller, MD. Management and outcome of a varicella exposure in a neonatal intensive care unit: lessons for the vaccine era. AJIC 2011

Key differences between infectious disease outbreak responses and typical emergency response training

• ID outbreak requires prolonged response-weeks to months

• Staff illness or need for re-assignment impairs response

• National notification and help from CDC may be appropriate –always go through state DOH first!

Theme 3: Always Be Integrating•Use “routine” outbreaks and exposures to practice and test integration into the facility emergency operations plan“Team of Teams: New Rules of Engagement for a Complex World ”, General Stanley McChrystal

Sir Arthur Conan Doyle, “His Last Bow: Eight Stories”