# Presentation: 108578

## CDC perspective on non-O157 Shiga toxin-producing E. coli (STEC) in the United States

- Patricia M. Griffin, M.D.
- Chief, Enteric Diseases Epidemiology Branch
- October 17, 2007

## E. coli that cause human gastrointestinal illness

- Shiga toxin-producing (STEC), also called Enterohemorrhagic (EHEC)
- Enteropathogenic (EPEC)
- Enterotoxigenic (ETEC)
- Enteroinvasive (EIEC)
- Other types, less well characterized

## E. coli that cause human gastrointestinal illness

- Shiga toxin-producing (STEC), also called Enterohemorrhagic (EHEC)
*E. coli *O157 serogroup
- Non-O157 serogroups
- Enteropathogenic (EPEC)
- Enterotoxigenic (ETEC)
- Enteroinvasive (EIEC)
- Other types, less well characterized

## Animals are the reservoirs for STEC	

- Cattle
- Other ruminants
- Other animals
- especially those who have contact with cattle

## Major modes of transmission of STEC to humans – how the fecal matter gets to the mouth	

- Food
- cattle products, e.g., beef, raw milk
- food contaminated with cattle or human feces e.g., lettuce
- Water
- Drinking water
- Recreational water
- Animal contact
- contact with farm animals, e.g. petting zoos
- contact with farm animals’ environment
- Person contact
- With the feces of infected persons

## Sequence of events in E. coli O157:H7 infection

**non-bloody diarrhea, abdominal cramps**

**bloody diarrhea**

*Mead. Lancet 1998*

**Notes:**
Sequence is similar in nonO157 stec except that only ~40% develop bloody diarrhea, and HUS is rare.  (see slides at back of talk for source of this info).  Source of the 8% dev hus is rowe’s study in alberta.

## Sequence of events in non-O157 STEC infection

**Sequence of events in non-O157 STEC infection**

**non-bloody diarrhea, abdominal cramps**

**Notes:**
Sequence is similar in nonO157 stec except that only ~40% develop bloody diarrhea, and HUS is rare.  (see slides at back of talk for source of this info).  Source of the 8% dev hus is rowe’s study in alberta.

## Compared to persons with E. coli O157 infection, 

**persons with non-O157 STEC have less severe illness**
**But non-O157 STEC include many serogroups, with varying virulence**
- some typically cause only mild diarrhea
- others can cause HUS and death

## Clinical lab testing for STEC

*E. coli* O157
- Unusual feature: does not ferment sorbitol
- streak stool specimen onto plate containing Sorbitol-MacConkey (SMAC) medium
- select clear colonies (others are pink)
- O157 strains agglutinate when O157 antisera is added
- Non-O157 STEC
- Lack unusual features, look like good *E. coli*

## Timeline of public health recommendations for STEC

| 1994 | E. coli O157 infection made reportable |
| --- | --- |
| 1995 | Commercial Shiga toxin enzyme immunoassay (EIA) introduced |
| 2000 | Non-O157 STEC infections made nationally reportable |

## Testing for non-O157 STEC using the Shiga toxin EIA

- Clinical lab cultures stool specimen in broth
- tests broth for Shiga toxin using EIA
- positive test could be O157 or non-O157 STEC
- Clinical lab can send Shiga toxin-positive broth to State Health lab
- State Health lab isolates STEC
- State Health Lab sends STEC to CDC
- CDC determines serotype

## 
After adopting the EIA, some clinical labs stopped testing for E. coli O157 using selective media
E. coli O157 outbreaks could be missed 
Some clinical labs discard Shiga toxin-positive specimens without obtaining an isolate, so
simply report “Shiga toxin positive” to doctor
serogroup not determined
E. coli O157 strains not identified and sub-typed for outbreak detection 
Non-O157 outbreaks less likely identified

- After adopting the EIA, some clinical labs stopped testing for *E. coli *O157 using selective media
*E. coli *O157 outbreaks could be missed
- Some clinical labs discard Shiga toxin-positive specimens without obtaining an isolate, so
- simply report “Shiga toxin positive” to doctor
- serogroup not determined
*E. coli* O157 strains not identified and sub-typed for outbreak detection
- Non-O157 outbreaks less likely identified

**Some challenges arising from use of the Shiga toxin EIA**

## How do we learn about non-O157 STEC?

- FoodNet conducts active surveillance
- Some clinical labs isolate non-O157 STEC
- strains are serotyped at CDC
- Some health departments are doing studies, e.g.,
- Minnesota
- Connecticut
- Outbreak investigations
- Studies of HUS

## How do we learn about non-O157 STEC?

- FoodNet conducts active surveillance
- Some clinical labs isolate non-O157 STEC
- strains are serotyped at CDC
- Some health departments are doing studies, e.g.,
- Minnesota
- Connecticut
- Outbreak investigations
- Studies of HUS

## FoodNet Catchment Area, 2007

- Catchment population 45 million persons
- (15% of U.S. population)

**California**

**Oregon**

**New Mexico**

**Colorado**

**Minnesota**

**New York**

**Connecticut**

**Tennessee**

**Georgia**

**Maryland**

## Pyramid of Surveillance

**Exposed to STEC**

**Person becomes ill**

**Person seeks care**

**Specimen obtained**

**Clinical lab tests for STEC**

**STEC isolated**

**Reported to health department & CDC **

## Pyramid of Surveillance

**Exposed to STEC**

**Person becomes ill**

**Person seeks care**

**Specimen obtained**

**Clinical lab tests for STEC?**

**STEC isolated**

**Reported to health department & CDC **

## Pyramid of Surveillance

**Clinical lab survey**

**Active surveillance**

## Percent of clinical labs screening all stools for E. coli O157

**FoodNet sites**

**National sample**

*Boyce, J Clin Micro 1995; Voetsch CID 2004; and  unpublished preliminary data*

**Western states outbreak**

**% of labs**

**66%**

## Percent of clinical labs that ever conduct on-site testing for STEC using EIA, FoodNet

**% of labs**

- 3%

- 9%

*Preliminary data*

**Notes:**
More labs in 99 survey

## Human isolates of non-O157 STEC, by serogroup, FoodNet sites, 2000-2006

**42 serogroups**
**<1.5% each**

**N=575 isolates***

- **preliminary data; an additional 54 isolates had missing O group information*

**83%**

**Notes:**
Similar to other years

## Number of non-O157 STEC identified in FoodNet sites, 2000-2006

## How do we learn about non-O157 STEC?

- FoodNet conducts active surveillance
- Some clinical labs isolate non-O157 STEC
- strains are serotyped at CDC
- Some health departments are doing studies, e.g.,
- Minnesota
- Connecticut
- Outbreak investigations
- Studies of HUS

## Human isolates of non-O157 STEC serotyped by CDC, by serogroup, 1983-2002

*Brooks, JID 2005;192:1422*

**N = 940 isolates**

- % of isolates

**55 O groups, **
**each **_**<**_**1%**

**Notes:**
Similar to other years

## Human isolates of non-O157 STEC serotyped by CDC, by serogroup, 1983-2002

*Brooks, JID 2005;192:1422*

**N = 940 isolates**

- % of isolates

**55 O groups, **
**each **_**<**_**1%**

- 70%

**Notes:**
Similar to other years

## Human non-O157 STEC isolates submitted to CDC by states, 1983-2001

**Human non-O157 STEC isolates submitted to CDC by states, 1983-2001**

**(N = 653 isolates)**

**1**

## Seasonality of human non-O157 STEC isolates submitted to CDC, 1983-2002  

**(N=940 isolates)**

*Brooks, JID 2005*

## Persons with HUS rarely had non-O157 STEC strains that produced only Shiga toxin 1

| STEC toxin profile | HUS 
(n= 21) | No HUS
(n=271) |
| --- | --- | --- |
| Only Shiga toxin 1 
 | 5% | 68% |
| Shiga toxin 2 
(+/- Shiga toxin 1)
 | 95%
 | 32% |
| Total | 100% | 100% |

***Overall, 61% of human non-O157 STEC produced only Shiga toxin 1***

*Brooks, JID 2005*

- Isolates with clinical information submitted to CDC, 1983-2002

## How do we learn about non-O157 STEC?

- FoodNet conducts active surveillance
- Some clinical labs isolate non-O157 STEC
- strains are serotyped at CDC
- Some health departments are doing studies, e.g.,
- Minnesota
- Connecticut
- Outbreak investigations
- Studies of HUS

## Surveillance for STEC in all diarrheal stools

- Lab A: urban

- Lab B: serves a semi-rural area with agriculture and dairy farms

**Minnesota**

**Lab B**

**Lab A**

*Medus, Besser, Hedberg, Bartkus, Juni, Smith, *
*EID Conference 2003*

## Proportion of STEC that were O157 or non-O157, human diarrheal stools, Minnesota, 2000-2002

**Urban**

**Semi-Rural **

*Juni, Besser, Hunt, Smith, Hedberg, Medus,Sullivan, Bartkus, unpublished*

- % of STEC

**Notes:**
This is ugly, looks better in ireland talk, also map needs fixing
John besser wrote: Patty, here are the data you requested. 
Urban (1995 - 2002):  n = 16573;  O157 = 76;  non-O157 = 80
Rural (2000 - 2002):   n = 5906;  O157 = 47;  non-O157 - 44

## How do we learn about non-O157 STEC?

- FoodNet conducts active surveillance
- Some clinical labs isolate non-O157 STEC
- strains are serotyped at CDC
- Some health departments are doing studies, e.g.,
- Minnesota
- Connecticut
- Outbreak investigations
- Studies of HUS

## Outbreaks of non-O157 STEC infections, U.S., 1990-2007

**N = 23 outbreaks**

*Data from 2007 are preliminary*

**No. outbreaks**

- Shiga toxin EIA available

- Non-O157 STEC reportable

## Serogroups of non-O157 STEC outbreaks, U.S., 1990-2007

| Serogroup | No. outbreaks |
| --- | --- |
| O111 (one outbreak also had O157) | 10 |
| O121 | 3 |
| O26 | 3 |
| O45 | 2 |
| O27, O103, O104, O153 | 1 each |
| O26 and O121 together | 1 |

*Data from 2007 is preliminary*

**Serogroups of non-O157 STEC outbreaks, U.S., 1990-2007**

- N = 23 outbreaks

## Serogroups of 23 non-O157 STEC outbreaks, U.S., 1990-2007

| Serogroup | No. outbreaks |
| --- | --- |
| O111 (one outbreak also had O157) | 10 |
| O121 | 3 |
| O26 | 3 |
| O45 | 2 |
| O27, O103, O104, O153 | 1 each |
| O26 and O121 | 1 |

*Data from 2007 is preliminary*

**Serogroups of 23 non-O157 STEC ****outbreaks, U.S., 1990-2007**

*Green shows most common serogroups of sporadic cases*

## Modes of transmission in non-O157 STEC outbreaks, U.S.,1990-2007

| Mode | No. outbreaks |
| --- | --- |
| Food | 11 |
| Person-to-person | 6 |
| Lake water | 3 |
| Animal contact | 2 |
| Undetermined | 1 |

**Modes of transmission in ****non-O157 STEC outbreaks, ****U.S.,1990-2007**

- (N = 23)

## Food vehicles in non-O157 STEC outbreaks, U.S., 1990-2007

| Food Vehicle | No. outbreaks |
| --- | --- |
| Salad bar | 1 |
| Salad and ice | 1 |
| Berries | 1 |
| Milk | 1 |
| Cider | 1 |
| Punch | 1 |
| Unknown | 5 |

- N = 11

## Human non-O157 STEC outbreaks reported to CDC, 1990-2007

**CT=1**

**3**

**2**

**2**

**1**

**1**

**2**

**1**

**1**

**1**

**1**

**1**

**1**

**Human non-O157 STEC outbreaks reported to CDC, 1990-2007**

**(N = 23 outbreaks)**

*Data from 2007 is preliminary*

**1**

**1**

**1**

**2**

## Outbreak of STEC O111 infections, cheerleading camp, Texas, 1999

- 55 persons with diarrhea
- most were teenage girls
- 18 had bloody stools
- 2 develped hemolytic  uremic syndrome (HUS)
- Transmitted by salad bar and ice

## How do we learn about non-O157 STEC?

- FoodNet conducts active surveillance
- Some clinical labs isolate non-O157 STEC
- strains are serotyped at CDC
- Some health departments are doing studies, e.g.,
- Minnesota
- Connecticut
- Outbreak investigations
- Studies of HUS

## National prospective diarrhea-associated (D+) HUS study, 1987-1991

- Enrolled adults and children with D+HUS
- Requested
- stool sample
- serum to measure antibodies to O157 lipopolysaccharide (LPS)

*Banatvala, JID 2001*

## Patients with both stool culture and serology results (N=55)

- 18% had no evidence of STEC infection
- 82% had evidence of STEC infection
- 98% of these had evidence of *E. coli* O157 infection
- 3 of 4 with non-O157 STEC isolated from stool also had antibodies to O157 LPS
- suggests that *E. coli *O157 may have caused their HUS

***U.S. National HUS Study, 1987-1991***

*Banatvala, JID 2001*

**Notes:**
Compared to those with STEC infection, those with no evidence of STEC infection
less likely had bloody diarrhea 
less likely had onset in warm months (48% vs 75%)
1 had pancreatic cancer

## The results of the national study suggest

*that the proportion of HUS cases *
*in the United States *
*caused by non-O157 STEC was small*

## Other studies of HUS with stool cultures

- Among HUS cases tested within 6 days of onset of diarrhea, proportion with *E. coli* O157:H7 isolated
- United States (25 cases)  96%                 *(Tarr, J Infect Dis 1990)*
- Canada (30 cases)  87%                        *(Rowe, Epidemiol Infect 1993)*

## Other studies of HUS with serology  

- Proportion of D+HUS cases with O157 LPS antibodies
- England:  73% *(Chart, Lancet 1991)*
- Central Europe:  73% *(Bitzan, Epidemiol Infect 1993)*
- France:  67% *(Decludt, Epidemiol Infect 2000)*

## Other studies 

*in the United States and other countries*
*have also reported that *
- E. coli *O157 is the major cause of HUS*

## CDC work to improve diagnosis of STEC infections

- Began a clinical diagnostics working group
- includes CDC, clinical labs, others
- Meetings
- May 2006
- January 2007
- Published MMWR with guidelines, September 2006

## Slide 48

## Clinical laboratories should strongly consider including STEC O157 in their routine bacterial enteric panel 

**Clinical laboratories should strongly consider including STEC O157 in their **_**routine**_** bacterial enteric panel **
**The best way to identify all STEC infections is to screen all stool samples.....for Shiga toxins**
**Laboratories that use a Shiga toxin EIA....should culture all positive broths....**
**When a Shiga toxin-positive broth does not yield STEC O157, the broth...should be quickly forwarded to the state...laboratory for identification of non-O157 STEC.**
**All non-O157 STEC...should be sent...to CDC.**

## Summary: non-O157 STEC in the United States

- Non-O157 STEC are a diverse group
- but ~75% of human infections are due to 6 serogroups
- Clinical illness due to non-O157 STEC
- includes diarrhea, bloody diarrhea, HUS
- less likely severe than *E. coli *O157

## Summary (continued)

- Most non-O157 STEC infections are not diagnosed
- few clinical labs test stools for Shiga toxin
- but use of the EIA has increased
- more non-O157 STEC illnesses and outbreaks detected
- Challenges in testing for STEC by EIA
- “Shiga toxin positive” is not sufficient
- Serogrouping is important
- Rapid identification of *E. coli *O157 is important for outbreak detection

## Summary (continued)

- STEC Diarrhea
- O157 and non-O157 STEC isolated with similar frequency
- STEC-associated HUS
- estimate <10% caused by non-O157 STEC
- strains that produce _only_ Shiga toxin 1 much less likely to cause HUS than strains that produce Shiga toxin 2
- 61% of human non-O157 STEC strains produced only Shiga toxin 1

## Contributors	

- State and local health departments
- Enteric Diseases Epidemiology Laboratory
- Many other collaborators

## Enteric Diseases Epidemiology Branch

**Enteric Diseases Epidemiology Branch**

## Thank you

- Conclusions and opinions expressed
-  herein are those of the presenter and
-  do not necessarily represent the views
-  and policies of  CDC and DHHS.