Goals for Today. Protecting, Maintaining and Improving the Health of All Minnesotans: The Bridges Between Clinical & Public Health

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1 Protecting, Maintaining and Improving the Health of All Minnesotans: The Bridges Between Clinical & Public Health Paula M. (Snippes) Vagnone MT(ASCP) Microbiology Supervisor MLS Program Advisor MDH-Public Health Laboratory Clinical Laboratory Collaborative Duluth, 20 Goals for Today Explain the changes in the revised Group B Streptococcal Guidelines Provide background - the MN Laboratory System Explain Carbapenem-resistant Enterobacteriaceae Describe an outbreak case study and discuss the CDC STEC guidelines Update on the current measles outbreak 2 Active Bacterial Core Surveillance (ABCs) Group B Streptococcal Disease Active Bacterial Core Surveillance (ABCs) Collaboration: CDC, State health depts., universities Active lab- and population-based surveillance for invasive bacterial pathogens of public health importance GAS, GBS, H. influenza, N. meningitidis, S. pneumoniae, MRSA Acknowledgement: Corrine Holtzman MDH Epidemiologist Photos courtesy of Dr. Lesley McGee, Dr. Richard Facklam CDC, ASM Microbe Library 4 Active Bacterial Core Surveillance (ABCs) Areas Meningococcal Disease (Neisseria meningitidis) all invasive disease Streptococcal Disease (all invasive disease caused by GAS, GBS, S. pneumo) 6

2 Incidence of Invasive GBS Disease MN Neonatal sepsis, < 7 days after birth (bacteria isolated from a sterile site, excluding coagulase-negative Staphylococcus) 7 8 Incidence of Invasive GBS Disease by Gender and Age Group, MN-2009 Invasive GBS Disease Cases and Deaths by Age Group, MN-2009 Characteristic Gender Cases (n=448) Incidence per 00,000 persons Male Female Age Group Under yr yrs yrs yrs yrs yrs yrs = early onset 4 = late onset yrs yrs yrs Age Group Cases Deaths % Died Under yr % -4 yrs yrs yrs % yrs % yrs. 3 3% yrs. 33 3% yrs % yrs % 70+ yrs. Total % 5% 0 Neonatal Sepsis-Invasive Disease in First Six Days of Life by Pathogen, MN (200) Incidence of Invasive Early and Late Onset GBS Disease, MN ( ) This chart represents 58 cases. 2 2

3 Early-onset GBS Disease in the U.S. st ACOG & AAP statements CDC draft guidelines published Consensus guidelines Universal screening 3 4 Early On-set GBS Disease Prevention - CDC 200 GBS Guidelines Cornerstone of the Recommendations: Late-antenatal screening (35-37 weeks gestation) for GBS colonization Background: Group B Streptococcus Disease Causes invasive disease in young infants, pregnant women and older adults Can cause serious illness and sometimes death Newborn infants Elderly Immunocompromised In 970s U.S., GBS emerged as most common cause of sepsis and meningitis in infants <3 months of age Mortality rate as high as 50% for early onset 5 6 Background: Maternal GBS Colonization Common colonizer of genital, GI tracts - women 0-30% of all women colonized Rates higher in African-American women Colonization difficult to detect clinically Asymptomatic Dynamic condition Cannot determine from history or physical GBS maternal colonization is a strong risk factor for early onset GBS disease in infants Labs Play a Critical Role in Success of Universal Screening Correct laboratory processing of specimens critical to the success of universal screening Most cases of early onset GBS disease now occur in infants born to women who screened negative (Van Dyke 2009; NEJM; 360: ) Due in part to false negative prenatal screening results To prevent as many cases as possible, it is important to optimize specimen collection and processing procedures 7 8 3

4 200 GBS Prevention Guidelines: Lab Methods that have NOT Changed Since 2002 Timing: 35 to 37 weeks gestation Vaginal-rectal swabs most optimal Enrichment step critical - greatly sensitivity ALL prenatal samples must be enriched in broth media for 8-24 hours ~50% of women will have a false negative result if sample is not incubated for 8-24 hours in enrichment broth 200 GBS Prevention Guidelines: Lab Methods that have NOT Changed Since total hours of incubation for subculture plate important for negative samples Higher likelihood of false negatives without 48 hours incubation Clindamycin susceptibility testing for PCNallergic women at high risk of anaphylaxis Studies have shown that samples from PCN-allergic women at high risk of anaphylaxis rarely undergo susceptibility testing Increasing rates of clindamycin resistance make testing extremely important for disease prevention 9 20 Key Changes for Labs 200 CDC GBS Guidelines Chromogenic media GBS identification options for prenatal specimens expanded to include: chromogenic media (plates, broth) Check incubated inoculated broth for color change. If color change present, report as GBS positive If color change NOT present: Important to realize that chromogenic methods may only identify beta-hemolytic GBS Must try to identify non-beta hemolytic GBS Key Changes for Labs 200 CDC GBS Guidelines Chromogenic media Pigmented Broth Positive color change 2 Photo courtesy of Dr. Lesley McGee, CDC 22 Key Changes for Labs 200 CDC GBS Guidelines Direct ID from Enrichment Broth Direct testing for GBS from broth can occur AFTER incubation in enrichment broth The following methods are supported for direct testing of the enrichment broth: DNA probe Latex agglutination test Nucleic acid amplification testing (NAAT) Key Changes for Labs 200 CDC GBS Guidelines PCR, Nucleic Acid Amplification Test (NAAT) Can be done only after enrichment in broth Very important for accuracy of result Enrichment lengthens time to final result, but accuracy is much more important for antenatal testing

5 Key Changes for Labs 200 CDC GBS Guidelines Reporting Bacteriuria 2002 guidelines required labs to report ANY quantity of GBS found in urine cultures Required great deal of lab time Studies of bacteriuria indicated the use of 0 4 CFU/mL as cutoff Difficult with available data to determine significance of lower colony counts 200 recommendation is to report positive urine cultures with 0 4 cfu/ml of GBS GBS Prevention: Intrapartum Antibiotic Prophylaxis (IAP) Clinical trials in 980s of IAP to prevent GBS disease IV penicillin or ampicillin Given to GBS-colonized women (+/- additional risk factors) Reduction in infant colonization & GBS disease Antibiotic Recommendations Intrapartum Prophylaxis Standard: Penicillin (PCN) or ampicillin Alternatives: PCN-allergic and low risk for anaphylaxis: cefazolin PCN-allergic but high risk for anaphylaxis depends on susceptibility to clindamycin & erythromycin If susceptible to clindamycin (including lack of inducible resistance) clindamycin If unknown or not susceptible vancomycin Key Changes for Labs 200 CDC GBS Guidelines - AST Test for inducible clindamycin resistance: on all isolates sensitive to clindamycin; and resistant to erythromycin; and from PCN-allergic women at high risk for anaphylaxis Clinda/Eryth Susceptibility Testing for GBS Room for improved implementation In a review of U.S. births in , 84% of mothers at high risk for penicillin anaphylaxis received clindamycin Only 8% had documented susceptibility testing (Van Dyke 2009; NEJM; 360: ) Susceptibility of GBS: ABCs Isolates, invasive isolates collected from 5 sites* All susceptible to penicillin, ampicillin, cefotaxime, and vancomycin, however: Erythromycin resistance: 46% Clindamycin resistance: 24% *For 2007, only early-onset isolates were tested

6 What about Resistance to Penicillin? Emergence of elevated MICs to β-lactams 2 ABCs isolates from different states and years ( ) 2 in MN Isolates are just at the susceptibility threshold; clinical significance is unclear Clinda & Eryth Resistance among GBS isolates ABCs sites, *Isolates are from CO, GA, MD, MN, NY, and OR data excluded 32 Intrapartum GBS Testing Some facilities can provide intrapartum PCR for GBS Enrichment step is not practical for intrapartum testing because of the delay in results Decreased sensitivity of test result without broth enrichment step Key Changes for Labs 200 CDC GBS Guidelines Intrapartum GBS Testig Can do intrapartum PCR testing directly on swabs (no-enrichment) for women who are GBS unknown at time of delivery who have no risk factors: Positive result: intrapartum antibiotic prophylaxis Negative result: No intrapartum antibiotic prophylaxis, unless risk factors develop GBS status at delivery Intrapartum NAAT Testing: Minnesota Laboratory System GBS + GBS - *GBS unknown IAP No IAP Risk Factors No Risk Factors If available, rapid nucleic acid amplification testing may be performed on patients with unknown GBS status who present at triage or labor/delivery with no risk factors. IAP NAAT + NAAT - IAP **No IAP An integrated network of public and private clinical laboratories working together to protect and improve the health of all Minnesotans **Unless risk factors develop

7 Goals of the MLS MLS Communication Enhance quality of microbiology practice Infectious disease outbreak detection Antimicrobial susceptibility surveillance Every-day disease detection Improve Emergency Readiness Bioterrorism Chemical terrorism Other public health emergencies 37 Communication MLS Lab Updates/Alerts [MLS: e-lab] Listserv 38 MLS Educational Resources Educational Resources Challenge Set CLSI Guidelines BT Binders LRN Sentinel Lab BT Wet Workshops Education and Training link Regional Conferences Foodborne Outbreaks FoodNet Active Surveillance Network Oregon California Colorado New Mexico Minnesota New York Connecticut Maryland Tennessee Georgia Acknowledgement: - Centers for Disease Control and Prevention - U.S. Department of Agriculture Josh Rounds - Food and Drug Administration MDH Epidemiologist 42 7

8 Goals of Surveillance for Disease Outbreaks Discover outbreaks rapidly Prevent on-going illness Find problems in the system Fix problems Keep an eye on trends in the system Two Primary Disease Outbreak Surveillance Mechanisms in MN Outbreak reporting foodborne illness complaint hotline public: FOOD ILL healthcare providers Reportable diseases individual reported cases are interviewed, exposures compared to other reported cases Report Immediately by Telephone Report Within One Working Day Reportable Bacterial Enteric Pathogen Surveillance in MN Isolates must be submitted to the MDH- Public Health Laboratory Real-time pulsed-field gel electrophoresis (PFGE) subtyping of certain categories of bacterial isolates at MDH-PHL Routine, real-time interviews of all cases done at MDH Pulsed Field Gel Electrophoresis (PFGE) Bacteria hour.5 hours Molten agarose Lysis DNA Pulse electrophoresis Enzyme digestion (XbaI).5 hours 8 hours 30 minutes

9 Interviewing Cases: MN Basic Philosophy Deer Season Interview all cases ASAP-before PFGE Collect details on specific exposures Dates Restaurant, grocery store names Brand names Open-ended food histories Follow-up interesting hypotheses aggressively Re-interview cases with specific questions, conduct trace-backs, food testing, etc. 49 December, 200 MDH received a report of 2 students from same class hospitalized with bloody diarrhea 2 students were enrolled in the same phy-ed/environmental science class at Andover HS Andover High School Outdoor Adventures Class Activity of butchering, cooking, eating deer 5 52 November 2-4, deer were shot and field dressed deer was harvested after being hit by a car

10 November 5 and 6, deer were brought to school provided by students Stored in a shed Ice in the body cavity and around hind quarters November 6, 200 Deer Butchered Butchered under the football stadium Butcher skinned, quartered and deboned each deer Venison was wrapped in plastic, covered with ice and stored overnight in shed A small number of students reported contact with the meat on this day November 7, 200 Student cut meat Students cut larger portions into cubes Wrapped meat in butcher paper and put in freezer Larger cuts of meat that were not used returned to students that had provided the meat November 22, 200 Venison thawed Venison was pulled out of freezer to thaw Put in 5-gallon buckets to marinade November 23, 200 Students made venison kabobs with bamboo skewers Grilled it on a gas grill Ate it Students were instructed to: Wear gloves Wash their hands after having contact with raw venison Butcher used new tools never used on beef 0% bleach solution was used after both days of cutting the venison (6 th and 7 th )

11 Case Definition: An Andover HS Outdoor Adventures Class student Developed diarrhea ( 3 loose stools in a 24-hr period) lasting 3 days; OR Bloody diarrhea that started after the Nov. 6 th class Students interviewed about: Illness history Food consumption Venison handling in class (52%) students interviewed 28 cases identified 6 laboratory confirmed STEC infections 20 students ill not meeting case definition Evidence of norovirus infections 6 lab-confirmed STEC infections 5/6 had only Shiga toxin by MDH PCR /6 negative for Stx grew non-o57 E. coli 2 hospitalized students = O03:H2 2 students = O45:NM ( also had norovirus) 2 students = isolates not typeable 22 cases not lab-confirmed Practice that were significantly associated with disease: Consuming undercooked or pink venison Not washing hands after contact with raw venison or cleaning on November 23 Not wearing gloves during November 7 class Students in 4 th period class more likely to become ill than students in st or 5 th period classes Cross-contamination Not washing hands after bare-hand contact with raw venison Using same plate for raw and cooked venison Same tongs used to handle raw and cooked Skewers could introduce contamination into interior of meat 65 66

12 Venison from 2 students homes positive for E. coli O03:H2 one positive for O45:NM Venison butchered at school No evidence of cross-contamination between venison and beef products Butcher s tools had never been used on domestic ruminants It is likely that one or more deer were colonized by non-o57 STEC Marinade process could have spread fecal contamination to large amounts of venison The first documented foodborne outbreak of non-o57 STEC from venison Changes in practice due to this outbreak School district decided to stop the practice of cooking and consuming venison in class Previous E. coli O57:H7 Outbreaks Involving Deer 995 OR outbreak traced to venison jerky 996 WA outbreak traced to unpasteurized apple cider Deer feces at orchard + for O Connecticut case report Case and venison + for matching O Prevalence of STEC in Deer Why STEC in Deer? Studies of O57 prevalence range from 0.25% (Nebraska) to 2.4% (Kansas) Non-O57 STEC 5% of deer sampled from MN and WI wildlife management areas Deer and cattle can inhabit the same environments

13 Possible Factors Contributing to Contamination Gut shot Contamination during field dressing Possible Factors Contributing to Contamination Environmental contamination during transportation Possible Factors Contributing to Contamination Stored in conditions promoting bacterial growth Possible Factors Contributing to Contamination Possible cross-contamination during butchering Marinated in 5 gallon buckets Challenges in Detecting non- O57 STEC Outbreaks Non-O57 STEC infections are under recognized Many clinical laboratories don t test for non-o57 STEC % of clinical labs in FoodNet study Outbreak may not have been detected through clinical testing alone Challenges in Detecting non- O57 STEC Outbreaks Non-O57 are sorbitol + E. coli O57 = sorbitol negative O57 will more likely lead to HUS than non-o57; may be some association with shigatoxin

14 Challenges in Detecting non- O57 STEC Outbreaks Confusion about + shigatoxin test meaning that the patient is + for shigella Only shigella that has shigatoxin is Shigella dysenteriae U. S. data most common non- O57 E. coli serogroups O26 (9-25%) O03 (4 8 %) O (3-7%) O45 (5-3%) O2 (6-7%) O45 ( %) MN data most common non- O57 E. coli serogroups E. Coli O57 culture-confirmed cases MN, ( ) O (27%) O03 (27 %) O26 (4%) Other types (32 %) 8 82 non-o57 STEC Reported MN, ( ) Percentage (n=23) Non-O57 ϰ 2 = 6.3 P =.0 ϰ 2 = 6.4 P = (n=8) (n=) (n=7) (n=9) (n=6) 2006 (n=24) Stx alone Stx2 alone Both toxins 2000 (n=23) 200 (n=22) 2002 (n=4) O (n=8) 2004 (n=5) 2005 (n=2) 2006 (n=4) Year of specimen collection

15 CDC STEC Recommendations for Laboratories Recommendations for Diagnosis of Shiga Toxin-producing Escherichia coli Infections by Clinical Laboratories MMWR Recommendations and Reports, October 6, CDC STEC Recommendations for Laboratories CDC STEC Recommendations for Laboratories Bottom Line Prompt accurate Dx of STEC infection is important Appropriate treatment early in the course of infection is key IV fluids May decrease the risk for serious complications Renal damage Improve patient outcomes 87 Prompt Lab ID is Essential for: Detecting new and emerging serotypes Effective and timely outbreak responses and control measures Monitoring trends in disease epidemiology 88 CDC STEC Recommendations for Laboratories Main Recommendation: All stools submitted for routine testing from patients with acute community-acquired diarrhea (regardless of patient age, season of the year, or presence or absence of blood in the stool) be simultaneously cultured for E. coli O57: H7 (O57 STEC) and tested with an assay that detects Shiga toxins to detect non-o57 STEC. 89 Challenge Set 200 Results: Std practice for labs performing non-cult/rapid Dx methods for detection of STEC (n=65) Response Non-cult/rapid Dx Shiga toxin test NOT performed Non-cult methods performed in conjunction with culture Non-cult methods performed only by special request-dr. Non-cult methods performed by normal reference lab only Stool Cx performed only if non-cult method is + for STEC/Shigatoxin Only non-cult method is performed no stool culture Frequency Count 40% % % 0 0.8% 7 3.% 2.5% Other.5% 90 5

16 Specimen Submission to MDH- PHL Measles Outbreak 20 Update Both Shigatoxin + and E. coli O57 + Growing plate best specimen Shigatoxin broth Send both if possible Pam Gahr, MPH Epidemiologist, Senior Vaccine Preventable Disease Surveillance Unit Minnesota Department of Health 9 Photo: Cynthia Goldsmith, CDC 92 Background: Measles Epidemiology in the U.S. National Measles Cases Before introduction of vaccine (963) approximately 500,000 cases annually 989, 2 nd dose recommendation 998, ACIP and AAP recommendation for school entry requirements Fewer than 50 cases reported each year * *VPD Surveillance Manual, 4 th Edition, 2008 Measles Chapter Background: Measles Epidemiology in MN Measles in MN, cont. Six cases in previous 5 years 2 imported (African adoptee, visitor from Kuwait) 2 international travel extensive domestic travel no travel or known exposure No transmission in MN from any of these cases Highly vaccinated population Most recent transmission within Minnesota occurred in 997 Three unrelated cases in

17 Minnesota Measles Cases Measles Outbreak 20, MN March 2 - measles confirmed in a 9 month old infant Index case 30 month old, US born, returning traveler from Kenya Rash onset on February Measles Outbreak 20, MN Confirmed Measles Cases by Rash Onset (Feb. 5 - April 24, 20) To date, 23 confirmed cases 2 linked to the 30 month old (8 total) age 4 months to 5 years old One case in an adult traveler who acquired infection in Florida (unknown vaccination status) One case in an adult traveler who acquired infection in India (vaccinated) One case with unknown exposure Case by rash onset date Case by specimen collection date (no rash) Non-outbreak cases Case with no known exposure February March April Date of Rash Onset Genotype Kenya B Exposure Settings for Outbreak Cases (n=2) Index case acquired infection in Kenya Drop-in Daycare (3 cases exposed) Hospital (3 cases exposed in E.D.) Household (4 cases exposed) B3 D4 D8 Orlando India?? 2 2 BLACK Travel Associated RED Shelters and 2 BLUE HealthCare Center GREEN Daycare Centers and 2 PURPLE Private homes - 3 Congregate living for the homeless (8 cases exposed) Daycare-2 ( case exposed) One unknown exposure

18 Laboratory confirmation for Outbreak Cases (n=2) Measles Genotypes 9 laboratory confirmed at MDH-PHL 2 epi-linked with clinical symptoms Genotyping at CDC and MDH revealed index case and linked cases are B3 Endemic in sub-saharan Africa Case exposed in Florida D4 Endemic in multiple locations Case exposed in India D8 Endemic in West Africa and India Distribution of measles genotypes associated with endemic transmission in various areas of the world based on information available in JID 2003; 87 (supp ) Rota and Bellini 04 Vaccination Status for Outbreak Cases (n=2) 7 cases were too young to receive vaccine 9 cases were of age but were not vaccinated case was vaccinated prior to the recommended age 4 cases have unknown vaccine status Vaccination Status for Non- Outbreak Cases One had unknown vaccination status One was vaccinated (2 doses) Hospitalizations for Outbreak Cases (n=2) 4 hospitalized 2 had dehydration Vomiting and diarrhea 2 also had pneumonia also had sepsis also had croup 7 also had otitis media Outbreak Control Efforts Exposed person follow-up: MMR for persons without evidence of immunity and w/in 3 days of exposure IG for persons without evidence of immunity and w/in 6 days of exposure Children 6- months living in selected congregate living facilities receive dose of MMR Children in Hennepin County and those of Somali descent receive early 2 nd dose of MMR

19 Conclusions: It s not over yet Most recent rash onset April 24 May 9 is the last day of current incubation period Continued monitoring of immunization status at affected exposure sites Immunity testing (IgG) for select exposure sites Continued specimen collection of suspect cases Measles outbreaks spread across Europe Copenhagen, 20 April 20 Thirty countries in WHO s European Region have reported a marked increase in measles cases, with 6500 so far in 20. Epidemiological investigations and genotyping by laboratories confirm exportation of the virus among several countries in the Region and to other regions of the world. Outbreaks and the further spread of measles are likely to continue so long as people remain unimmunized or do not get immunized on time according to the routine immunization schedule. France faces the largest outbreak, with 4937 measles cases officially reported from January to March 20, a figure almost equal to the total of 5090 cases reported for whole of Paula M. Vagnone Program Advisor - Minnesota Laboratory System (MLS) Supervisor Clinical Microbiology Laboratory MDH Public Health Laboratory paula.snippes@state.mn.us 9