Contact Investigation San Antonio, Texas January 14-15, 2013

Contact Investigation San Antonio, Texas January 14-15, 2013 Detecting and Handling a TB Outbreak Jessica Quintero, BAAS January 15, 2013 Jessica Quintero, BAAS has the following disclosures to make: No conflict of interests No relevant financial relationships with any commercial companies pertaining to this educational activity 1

Detecting and Handling TB Division of Tuberculosis Elimination, CDC Terminology and Background 2

Question How would you define a TB outbreak? More than expected number of cases Transmission continues Work exceeds capacity More than one contact found to have TB disease Additional cases with unexpected epi links 3

Our Working Definition of a TB Outbreak More cases than expected, cases linked, evidence of ongoing transmission and Work needed to control outbreak exceeds TB program s usual capacity Outbreak vs. Cluster Terms sometimes used interchangeably Must differentiate when say cluster Group of epi-linked cases Genotype cluster Our teams prefer to reserve term for this 4

Our Experience from TB Outbreak Investigations, 2005 2008 U.S.-born, males, and substance abuse characterized most outbreaks Prolonged infectiousness was the most frequent contributing factor Drug-use locations were often sites of TB transmission during outbreaks Source: Review by K Mitruka, CDC, 2009 Outbreak Prevention: What Works (1) Helping providers to think TB and communicate early and often about suspect TB cases with you 5

Outbreak Prevention: What Works (2) Every case was once a contact Careful & complete contact investigations prevent outbreaks Easier when contacts primarily within a family More difficult when incarcerated, drug-using, homeless, or transient TB Outbreak Investigation Conceptually, just several overlapping contact investigations, but with a greater emphasis on data management and contact prioritization 6

Contact vs. Outbreak Investigation Short-term investigation activities very similar But with outbreak, more long-term activities More contact investigation and follow-up Greater need to ensure treatment completion Continuing education of providers, patients Ongoing surveillance, use of genotyping Source: CDC s 2005 Controlling TB in the United States Program Manager Roles in TB Outbreak Investigations Guide transition from usual contact investigation to outbreak investigation mode Shift work assignments, personnel, resources Identify & communicate any needs for additional resources Ensure activities are assigned and completed Coordinate internal and external communication 7

TB Outbreak Detection Detecting Contact investigation findings suggestive of outbreak 8

Contact Investigation Findings that Are Suggestive of an Outbreak TB disease* in any contact who was not identified or who had until then been considered low priority Unexpectedly high number of contacts with TB disease* or LTBI, especially if documented negative-to-positive TST / IGRA TB disease* or LTBI in contact <5 years *Would expect genotypes, if avail, to match Usual TB Contact Investigation Case Contact Not unusual to have one TB case found in high-priority contacts perhaps one of Sue s close friends 9

A Concerning Contact Investigation (1 of 2) Case Contact >1 contact found to have TB disease what if three friends had TB? A Concerning Contact Investigation (2 of 2) Case Contact or An initially unidentified contact later found to have disease Waffle House customer 10

Detecting Contact investigation findings suggestive of outbreak Can use genotype results to help evaluate whether an outbreak The Usual Order 1. Start with the patients 2. Interview and learn about epi links 3. Genotyping just confirms those links 11

We Expect Epi-linked Cases to Have Matching PCRTypes Sue and her 3 friends and the Waffle House cook and customer Detecting Contact investigation findings suggestive of outbreak Unexpected number of cases for time and place or increase in cases with some commonality Can again use genotype results to help evaluate whether an outbreak 12

EXAMPLE A Bad Month Three female coworkers on night shift at a casino all diagnosed with TB One woman s boyfriend also diagnosed with TB All within one month Do you think this is an outbreak? 13

Genotyping Results Patient PCR Type State Cluster Employee 1 PCR06883 n/a Employee 2 PCR06859 n/a Employee 3 PCR04231 n/a Boyfriend PCR03167 n/a Do you still think this is an outbreak? One More Step 14

Genotyping Results Patient Spoligotype MIRU Employee 1 076177607760771 224326133223 Employee 2 777777777420771 227225112222 Employee 3 777777777760771 224325152224 Boyfriend 777776777760601 225325153222 completely different Summary and Take-Home Point Completely different genotypes: not same chain of transmission Crazy coincidence, but not an outbreak Four simultaneous contact investigations Three involving same congregate setting 15

Detecting Contact investigation findings suggestive of outbreak Unexpected number of cases for time and place or increase in cases with some commonality Unexpected numbers of TB cases with same genotype and some other connection Geographic, temporal, risk factor Basic Concept of Genotyping Outbreak Detection Genotypes that match (cluster) are likely to be in the same chain of transmission But chain of transmission may be very old and clusters are not always outbreaks So how do we determine which clusters might actually be outbreaks? 16

Cluster Genotype Cluster PCR00063 PCR00063 PCR00063 PCR07422 PCR00063 PCR00428 PCR00881 PCR00063 PCR10277 PCR00881 PCR00881 PCR00063 17

Using Genotyping to Detect a.k.a. Reversing the Approach 3. Matching genotypes 2. Look at the patients in the cluster 1. Reinterview patients, find epi links Using Genotyping to Detect Volume of Information 3,147 county-level genotype clusters from August 2007 to August 2010 2+ cases with matching genotypes in a single county 18

Using Genotyping to Detect Goals Identify genotype clusters that are, or have potential to become, outbreaks Differentiate from ones representing remote or endemic transmission, or just the underlying populations Prioritize clusters for response Optimally use available information Using Genotyping to Detect Framework 1. Cluster detection / alerting 2. Cluster assessment Use available info to determine Likelihood of recent transmission Current level of concern to public health Whether opportunities to intervene 3. Cluster investigation with patient reinterview 4. Outbreak investigation existing data new data 19

Using Genotyping to Detect Framework 1. Cluster detection / alerting 2. Cluster assessment Use available info to determine Likelihood of recent transmission Current level of concern to public health Whether opportunities to intervene 3. Cluster investigation with patient reinterview 4. Outbreak investigation Using Genotyping to Detect Ways to Alert and Monitor Routine review of all genotype clusters Feasible in some low-incidence jurisdictions Routine review of selected clusters Based on past history (e.g., known outbreaks) Ad hoc review of flagged clusters Flagged because of risk factors, geographic concentration, or cluster growth Locally generated algorithm or TB GIMS ALERT 20

TB GIMS Alert Level Calculated automatically by TB GIMS Measures geographic concentration* of a genotype Compares county to national distribution Over most recent 3 years * based on log-likelihood ratio TB GIMS Alert Level 21

TB GIMS Cluster Snapshot TB GIMS Alert Level Automatic email notifications* to TB GIMS users when a cluster alert level has increased from None to Medium from Medium to High * starting November 2010 22

Using Genotyping to Detect Volume of Information 3,147 county-level genotype clusters from August 2007 to August 2010 252 with Medium or High TB GIMS Alert (less than 1%) Using Genotyping to Detect Framework 1. Cluster detection / alerting 2. Cluster assessment Use available info to determine Likelihood of recent transmission Current level of concern to public health Whether opportunities to intervene 3. Cluster investigation with patient reinterview 4. Outbreak investigation 23

Does this Cluster = Outbreak? 4 TB patients clustered in a county (PCR12345) Note: fictitious data for training purposes 3 U.S.-born Blacks 1 U.S.-born White Cluster Assessment Use TB GIMS reports, other available records, and local TB program knowledge to assess Person Demographics and risk factors of patients in this cluster? Place Where else is this genotype found? Is it common? Time When were the most recent cases? Genotype Do the MIRU2s match? How similar are the genotypes? 24

TB GIMS Reports 49 Interpreting Cluster Information Based on available info, determine Likelihood of recent transmission Is this one still hot? Current level of concern to public health How should we prioritize further investigation? Whether opportunities to intervene Could we do something about this? What additional info do you need to answer the above? What would you do next? 25

EXAMPLE images: SamPac (2006), Mark Hawthorn (2010), Eric Pouhier (2005) TB GIMS Email Alert FROM: TB GIMS TO: Dr Patrick Moonan SUBJECT: TB Genotype Cluster Alert Tarrant County, RB, PCR01047 This message is to notify you that the genotype cluster PCR01047 in Tarrant County, TX has an increased Alert. To review data on this genotype cluster, log in to TB GIMS. An increase in alert level indicates increased geographic clustering of a genotype in a specified county as compared to the rest of the United States, and might be a indicator of recent transmission of TB. If you have any questions about this message, please contact your state TB control program. If you have any questions about TB GIMS, please email the TB GIMS help desk at tbgims@cdc.gov. 26

Using Genotyping to Detect Framework 1. Cluster detection / alerting 2. Cluster assessment Use available info to determine Likelihood of recent transmission Current level of concern to public health Whether opportunities to intervene 3. Cluster investigation with patient reinterview 4. Outbreak investigation existing data new data TB Outbreak Response 27

Basic Steps of a TB Outbreak Response Basic Steps of a TB Outbreak Response 1. Confirm outbreak 2. Case definition 3. Existing data review & analysis 4. New data and reinterviews 5. Plan response 6. Implement plan 7. Examine findings & decide next steps 8. Implement steps 9. Evaluate response 10. Close the investigation 28

Step 1. Confirm Existence of an Outbreak Surveillance More cases than expected for time and place Genotyping Culture-positive cases have matching patterns Epidemiology Cases are epi-linked, transmission continues Non-Outbreak Reasons Why Might See Sudden Increase in Number of Cases More people Influx of immigrants with higher TB risk More reporting Providers with heightened awareness More diagnoses Provider or laboratory changes 29

Non-Outbreak Reasons Why Might See Sudden Growth in Genotype Cluster Greater participation in NTGS That jurisdiction submitting more isolates for genotyping Hospital, local health dept, etc. NTGS lab (in MI or CA) TB isolate State lab Step 2. Define Outbreak Case Epidemiologic criteria: use to On geographic area of greatest impact Only as far back in time as practical Refine further with genotyping results Can still include clinical (culture-negative) cases if epi-linked to other outbreak cases 30

Example: Outbreak Case Definition Person & Place Time Genotype Epi links Tarrant County resident with TB in 2009 2010 PCR01047 (TX_0161) Or, if not genotyped, an epi link to a patient already included Typical Starting Point for Outbreak Case Definition 1. Exclude cases with different PCRTypes 2. Include cases with matching PCRTypes 3. Include epi-linked cases 31

Typical Ending Point for Outbreak Case Definition cases that can be linked only by genotype Possible Cases Definite Outbreak Cases cases that are both genotype- & epi-linked clinical or culture-neg cases with epi links Probable Cases Basic Steps of a TB Outbreak Response 1. Confirm outbreak 2. Case definition 3. Existing data review & analysis 4. New data and reinterviews 5. Plan response 6. Implement plan 7. Examine findings & decide next steps 8. Implement steps 9. Evaluate response 10. Close the investigation 32

Step 3. Review Case Medical Records Similar to review for contact investigation Same data management principles Simple, systematic, and safeguarded Decide early on which additional variables absolutely essential for outbreak investigation Open envelope F Homeless Outbreak Descriptive Epi 33

Patient Characteristics (N=10) Characteristic Age range Male Homelessness Excess alcohol use Illicit drug use Incarceration history n 2 to 68 years 9 (90%) 7 (70%) 8 (80%) 5 (50%) 6 (60%) Disease Characteristics (N=10) Characteristic n (%) Culture-confirmed with 8 (80) PCR01047 genotype Pulmonary 9 (90) Cavitary 2 (20) AFB smear-positive 4 (40) HIV infection 4 (40) 34

Basic Steps of a TB Outbreak Response 1. Confirm outbreak 2. Case definition 3. Existing data review & analysis 4. New data and reinterviews 5. Plan response 6. Implement plan 7. Examine findings & decide next steps 8. Implement steps 9. Evaluate response 10. Close the investigation Step 4. Re-Interview Outbreak Patients When did symptoms start? How linked to other cases in outbreak? Who were contacts during infectious period? What were locations frequented? Often necessary to interview patient multiple times 35

Need 10 Volunteers Homeless Outbreak It s Time to Connect the Dots Need to Connect the Dots: How Are Outbreak Patients Related? Describe the development of the outbreak Often helps to bring whole team together to draw it May lead to discovery of transmission sites and additional contacts 36

Shared Locations Drop Inn Source Pt 2 Krash Pad Hospital Pt 6 1 2 5 2 6 Home 1 4 5 7 8 Snapper Interiors Jail 2 3 2 7 10 6 9 EXAMPLE 2 To read more: Buff A, et al. article in Public Health Reports July Aug 2009, Volume 124, pages 490 494 37

A Bad Summer Four female adults and two children with culture-confirmed TB All with definite epi links Index patient was recently incarcerated with one of the four adults She shared households with rest after release Do you think this is an outbreak? Genotyping Results Patient PCR Type State Cluster 1 Index PCR05689 CT_019 2 Adult PCR05689 CT_019 3 Child PCR05689 CT_019 4 Adult PCR02931 CT_014 5 Adult PCR02931 CT_014 6 Child PCR02931 CT_014 Do you still think this is one outbreak? 38

Genotyping Results Patient Spoligotype MIRU 1 Index 777776407760601 224225154322 2 Adult 777776407760601 224225154322 3 Child 777776407760601 224225154322 4 Adult 777776407760601 224225153322 5 Adult 777776407760601 224225153322 6 Child 777776407760601 224225153322 very slight difference Summary Two clusters both part of same outbreak Occasionally in a single transmission chain, you can see minor changes in TB DNA 39

Take-Home Point When TB cases are definitely epi-linked, but don t seem to be in same genotype cluster, take a second look at the spoligo and MIRU If very different, probably unrelated If slightly different, call us to discuss Spectrum of TB Outbreak Assistance Available from CDC first point of contact is FSEB field consultant Telephone Onsite epidemiologic Temporary or email assistance program consultation assistance (personnel, extra $$) 40

Basic Steps of a TB Outbreak Response 1. Confirm outbreak 2. Case definition 3. Existing data review & analysis 4. New data and reinterviews 5. Plan response 6. Implement plan 7. Examine findings & decide next steps 8. Implement steps 9. Evaluate response 10. Close the investigation Need to Prioritize Contacts for Assessment Screening large numbers of people is rarely indicated Conceptually, just several overlapping contact investigations, so remain consistent with usual prioritization in 2005 contact investigation guidelines 41

Just Like in a Contact Investigation (1) Highest priority to contacts identified as possibly having symptoms of TB Next priority to contacts who If infected, are at high risk for progression to TB disease Age <5 yrs Weakened immune system (e.g., HIV) Had the most exposure As defined by that investigation Just Like in a Contact Investigation (2) Re-examine priorities throughout the investigation as findings are analyzed Decide whether to change focus Do not expand to additional contacts if doing so compromises your follow-up of known contacts In a contact or outbreak investigation, the decision to test a contact should be considered a commitment to offer treatment unless there is a compelling reason not to 42

Just Like in a Contact Investigation Special Situations Use location-based & traditional name-based approach for hard-to-reach populations e.g, homeless persons, substance users Diagnose TB and LTBI in persons at key locations or hotspots associated with outbreak e.g., homeless shelter, bar, drug house Drop Inn Contacts 46 Contact Prioritization in Homeless Outbreak All Other Locations 59 Tested 27 Not Tested 19 Tested 30 Not Tested 29 TST Positive 15 (56%) Outreach & treatment priorities TST Positive 7 (23%) Relative risk = 2.4 95% CI = 1.2 4.9 43

Need to Find and Assess Contacts Often the most challenging programmatic aspect of a TB outbreak investigation Additional resources and personnel for outreach Elements TB symptom review, with low threshold for ordering CXR and sputum (active case-finding) Consider IGRA (& simultaneous HIV test) if high-risk contact unlikely to return for TST read Basic Steps of a TB Outbreak Response 1. Confirm outbreak 2. Case definition 3. Existing data review & analysis 4. New data and reinterviews 5. Plan response 6. Implement plan 7. Examine findings & decide next steps 8. Implement steps 9. Evaluate response 10. Close the investigation 44

When Will This Be Over? Active case finding completed, no additional cases Identified contacts have been evaluated Both outbreak cases and contacts with LTBI have completed treatment Program gaps that contributed to outbreak addressed Ongoing surveillance to detect future resurgence Growing genotype cluster may be first hint there are more outbreak cases Program Manager Roles in TB Outbreak Investigations Guide transition from usual contact investigation to outbreak investigation mode Shift work assignments, personnel, resources Identify & communicate any needs for additional resources Ensure activities are assigned and completed Coordinate internal and external communication 45

Spectrum of TB Outbreak Assistance Available from CDC first point of contact is FSEB field consultant Telephone Onsite epidemiologic Temporary or email assistance program consultation assistance (personnel, extra $$) Onsite TB Outbreak Investigations 2002 2011 46

Onsite TB Investigations 2010 May June July Sept Oct Nov INH-resistant TB outbreak in homeless TB outbreak in homeless TB outbreak in adult psychiatric residence ongoing TB outbreak in homeless & incarcerated MDR TB outbreak TB outbreak in homeless Onsite TB Investigations 2011 Feb Mar Apr June July Oct TB outbreak in federal prisons TST conversions in hospital TB outbreak in homeless TB outbreak in rural community TB outbreak in rural community TB outbreak among healthcare workers 47

Other Follow-Up Assistance Available from DTBE Outbreak assistance funds to implement recommendations made by Epi-Aid or tech assist TB CoAg supplement via FSEB consultant May be used for short-term personnel, incentives/enablers, other services Temporary assignment of CDC PHAs May help train local staff, especially new hires Assist in instituting TB control practices Can conduct thorough program review if requested Spectrum of TB Outbreak Assistance Available from CDC first point of contact is FSEB field consultant Telephone Onsite epidemiologic Temporary or email assistance program consultation assistance (personnel, extra $$) 48