# Presentation: 094225

- Laboratory Response CapacityCoordinating Center for Infectious Diseases

**J. Michael Miller, Ph.D., (D)ABMM**
**Associate Director for Science**
**National Center for Zoonotic, Vector-borne, and Enteric Diseases**

## Each National Center responsible for different organisms.

**Each National Center responsible for different organisms.**
**No central, core facility to receive/triage calls regarding outbreaks.**
**Central specimen receiving located in NCPDCID.  Log in; deliver.**
**Response may be focused or distributed.**
**Collegial relationships critical to success.**

## CCID Laboratory Capacity

- Fifteen of 21 Divisions have laboratory activities
- >1000 laboratories within CCID
- 43 additional within NCEH
- Surge capacity is robust within CCID
- Estimate 40% of CCID’s ~4500 employees and contractors are laboratorians
- 80-85 CDC-Atlanta laboratories are registered for Select Agent work

## Laboratory Response Activities Within CCID

- Outbreak surveillance and response
- Reference identification capacity
- Public health research and applications
- Pathogen discovery
- Vaccine discovery and adverse event tracking
- Repositories
- Preparedness and response to all public health emergencies – a hallmark of our Mission
- Laboratory support
- Training (at CDC and in the field)
- Methods
- Products (test development and deployment)
- Service

## Laboratory Partners

- Primary clients: State Public Health Agencies
- World Health agencies
- Other Federal/State agencies
- Private sector; non-government organizations
- Academia
- Medical community
- Others with public health mission

## Previous Outbreaks of Unknown Etiology

- Respiratory disease in attendees of an American Legion convention in Philadelphia in 1976
- Early ’80s, acquired immunodeficiency syndrome initially emerges in men who have sex with men
- Severe acute respiratory syndrome in 2002-2003
- Severe pulmonary disease in the four-corners region of the U.S.
- Febrile illness; rash illness; encephalitis illness; jaundice, infectious diseases from transplants; unexplained deaths
**Many of these were caused by novel etiologic agents** that are now fully characterized

## Challenges of Outbreaks of Unknown Etiology	

- 25% to 50% of cases of acute respiratory illness
- 50%-75% of cases of encephalitis
- 25% to 50% of cases of acute gastroenteritis
- Brainerd diarrhea
- Noncultivable pathogens
- Crohn’s disease
- Jaundice
- Non-A-E viral hepatitis
- Isolates that resist identification or characterization
- Unexplained deaths

## Laboratory Tools  Used in CCID 

**Culture****	****	****	****	****Cell culture**
**Phenotypic analysis****	****	****	****Serology**
**Immuno-capture ****	****	****	****Western Blot****Immunohistochemical analysis****	****Histopathology**
**Electron microscopy****	****	****	****Mass spectroscopy**
**PCR assays for specific pathogens****	****Panviral PCR detection**
**Real time PCR assays****	****	****Random primer amplification**
**DNA sequencing/analysis****	****	****Parallel tag Sequencing **
**Microarrays ****	****	****	****	****“Fingerprinting” technologies**
**Generic enzyme function ****	****	****Target enrichment from specimens Proteomics **
**Primer Extension Enrichment Reaction (PEER)**
**Serum probe of translated-subtracted RNA**

## CDC’s Unique Roles 

- Many external experts and groups contribute to Public Health and medical research and practice
- CDC has a unique role in public health and emergency public health response
- Assess National and International events with a broad based expertise
- Deploy investigative teams
- Mobilize resources as needed for surge capacity
- Apply pathogen discovery tools
- Temporal data analysis with redirection
- International reference laboratories and repositories
- Extensive specimen inventory and data banks

## How the “average” outbreak is handled in CCID

**A call is made from a State or International public health agency requesting help and describing specific symptoms and the population affected.  **
**The call is usually directed to one of a number of scientific areas within CCID that addresses diseases and outbreaks with similar symptoms; i.e. pneumonia, diarrhea, rash illness, etc.  to different Centers and Divisions, depending on the primary symptom.**
**The group receiving the call assembles colleagues from multiple CCID sites as necessary.  A leader collaboratively integrates work between individual laboratories and a plan is instituted on how to work together to achieve closure to the outbreak**
**Consideration of etiology and future studies is by SMEs with clinical, epidemiologic, and laboratory expertise and uses available data from each discipline**
**In most cases, multiple etiologies must be considered and work is done in parallel or sequentially among multiple laboratories**

**A “manual” process; not automated.**
**Human interaction critical**
**Work often conducted in parallel with needed data exchange**

## Examples of Surveillance Tools for Foodborne Outbreaks

- FoodNet** ****(**Foodborne Diseases Active Surveillance Network)
- Conducts population-based, active surveillance for laboratory-confirmed infections caused by 9 pathogens commonly transmitted through food
*Campylobacter* spp., *Listeria monocytogenes*, *Salmonella* spp., *Shigella* spp., STEC O157, *Vibrio* spp., *Yersinia enterocolitica*, *Cryptosporidium* spp., *Cyclospora* spp.
- NARMS (National Antimicrobial Resistance Monitoring System)
- Conducts integrated surveillance to monitor the development of antimicrobial drug resistance among enteric pathogens from humans (CDC), foods (FDA), and animals (USDA)
- PulseNet USA
- Standardized molecular typing of foodborne disease-causing bacteria by pulsed-field gel electrophoresis (PFGE)
- OutbreakNet
- Network of state and federal public health officials who investigate foodborne disease outbreaks;  Epidemiologists, microbiologists, regulatory officials in 50 states; Long-standing collaboration formalized
- NEDSS (National Electronic Diseases Surveillance System)
- Effort to standardize and streamline surveillance for individual cases of nationally reportable diseases – Struggling, not yet successful
- From eFORS to Outbreak Reporting System (ORS)
- Will incorporate foodborne, waterborne and other enteric outbreak reporting (including norovirus) into one system – enhance user interface

**All require complex IT interactions but are not interconnected: data entry, tracking, reporting, access**

## Challenges We Face in Laboratory Response

- Resolving outbreaks of unknown etiology
- GMP development of assays in a “non-manufacture” arena
- FDA approval of public health assays (surveillance vs diagnostic) within a timely manner – especially emergency items
- Competing resources results in reduction of laboratory capacity and response
- Recruitment and retention of top laboratory scientists
- Developing the next generation of public health leaders
- Complexity of electronic communication needs
- Integrating critical public health information and tracking in a secure, efficient, and accessible format.