Epidemiological Methods in TB
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1 Responding to a TB Event San Antonio, Texas April 29-May 1, 28 Epidemiological Methods in TB Lynelle Phillips, RN, MPH April 29, 28 Epidemiological Methods in TB Lynelle Phillips, RN MPH Heartland National TB Center April 29,28 1
2 2
3 Why do outbreaks happen? When a contact investigation around a source case fails to break the chain of transmission No contact investigation (13%) Contacts missed (12%) Contacts lost to follow-up (27%) Contacts not treated/incomplete treatment (approx. 5%) Refused MDR/XDR Do not complete treatment Reichler, M. R., R. Reves, et al. (22). "Evaluation of investigations conducted to detect and prevent transmission of tuberculosis.[see comment]." JAMA 287(8): Why do outbreaks happen? (2) Common elements Delayed diagnosis for 1 or 2 key spreaders Low index of suspicion of providers TB case not forthcoming with symptoms Risky location facilitated transmission Risky behaviors facilitated transmission Contacts not identified in time to intervene Contacts at high risk for progression to disease (HIV) Highly infectious TB case (laryngeal) 3
4 Why do outbreaks happen? (3) Challenging populations TB cases refuse to name contacts TB cases distrust government officials TB cases with different culture, language, race, ethnicity Outbreak terminology Source case started the outbreak Index case first case to be reported to the health department Secondary case infected by exposure to source case 4
5 # s k i n t e s t c o n v e r t o r Case #1 56 inmates 6 staff TST convertors Prison outbreak 4 2 # of cases Aug- Sep- Oct- Nov- Dec- Jan-1 Feb-1 Mar-1 Apr-1 May-1 Jun # s k i n t e s t c o n v e r t o r inmates 6 staff convertors Case #1 Sputum screening Case #2 Prison outbreak (2) Aug- Sep- Oct- Nov- Dec- Jan-1 Feb-1 Mar-1 Apr-1 May-1 Jun # of cases 5
6 8 6 # sk i n t e st c o n v e r t o r inmates 6 staff convertors Sputum screening Case #1 Case #2 Prison outbreak 3 month follow up 33 inmate convertors Case #3 Case #4 3-month follow up 13 inmate convertors Aug- Sep- Oct- Nov- Dec- Jan-1 Feb-1 Mar-1 Apr-1 May-1 Jun-1 Outbreak investigation purposes Break the chain of transmission Active case finding Treat infected contacts Ensure completion of treatment Learn about TB transmission dynamics Previously unknown risk factors Factors contributing to outbreak Programmatic interventions to prevent outbreaks in the future 6
7 Overview of epidemiology Epidemiology The study of the distribution and determinants of health-related states in specified populations, and the application of this study to control health problems. Epidemiology Descriptive epidemiology - examine the distribution of diseases in the population person (who gets the disease) place (where they get the disease) time (when they get the disease) HYPOTHESIS GENERATING Analytic epidemiology study the relationship between risk and disease HYPOTHESIS TESTING 7
8 Descriptive epidemiology Active surveillance health agency initiates data collection Targeted TST Contact investigations Passive surveillance health care providers are required to report information to the health department RVCT/TIMS TB Case Rates by Area cases per 1, Missouri St. Louis County St. Louis City Kansas City Spfd/Grn
9 TB Case Rates by Area cases per 1, Missouri St. Louis County St. Louis City Kansas City Spfd/Grn TB Case Rates by Area cases per 1, Missouri St. Louis County St. Louis City Kansas City Spfd/Grn
10 Analytic epidemiology The search for causes and other factors that influence the occurrence of health-related events (e.g. The why? And How?) The process of assessing whether groups with different rates of disease have differences in demographic characteristics, genetic or immunologic makeup, behaviors, environmental exposures, etc. Gregg, MB (22) Field Epidemiology 2 nd Ed. Oxford Press University Press New York, NY p.9 Analytic epidemiology (2) To identify risk factors for primary multi-drug resistant TB (P-MDRTB), a case control study was conducted in February 1999 of never-treated, smear- and culturepositive TB patients reported during October October A case of P-MDRTB was defined as culture-confirmed MDRTB in a patient; controls were patients with culture-confirmed drug susceptible TB.compared with controls, case-patients were significantly more likely to have a history of homelessness (23% versus 5%; OR=3.1; 95% CI= ; p=.4) MMWR 1991;48:
11 Relative Risk Relative risk a comparison of the risk of a health problem in 2 groups Useful in prioritizing contacts in large investigations and outbreaks High Medium Low 2 x 2 table Exposure yes Exposure no Disease yes a c Disease no b d Relative Risk = a/a+b c/c+d 11
12 Data from investigation Persons tested # of students tested # of students TST positive Relative Risk All students
13 Persons tested All students Data from investigation # of students tested 559 # of students TST positive 58 Relative Risk Students in 1 class x 2 table high school outbreak TST RESULTS EXPOSURE GROUP positive negative TOTAL In class with index case Not in class with index case TOTAL TESTED RR = 25/16 = 3.2 (CI = ) 33/453 13
14 Data from investigation Persons tested # of students tested # of students TST positive Relative Risk All students Students in 1 class Students in periods 1,2, Persons tested All students Data from investigation # of students tested 559 # of students TST positive 58 Relative Risk Students in 1 class Students in periods 1,2, Students in 3 classes Phillips L, Carlile J, Smith D. Epidemiology of a TB outbreak in a rural MO high school. Pediatrics. 24;113:e
15 High, medium, low risk contacts In > 2 classes RR = 5.7 Index case In classes 1,2,5,6,7 RR =4.2 In > 1 class RR = 3.2 Steps in disease investigation Verify the diagnosis/case definition Establish the existence of an epidemic Make a quick survey of known cases and the community situation Formulate a tentative hypothesis Plan/Conduct a detailed investigation Analyze the data Test Hypothesis Formulate conclusions Implement control measures Make report After action review 15
16 Verify the diagnosis Develop a case definition TB Disease Culture confirmed Clinical case Genotype MDR/XDR Know the current definitions LTBI Close contacts >5mm induration Establish the existence of an outbreak 16
17 Epi curve Kansas City KS/MO homeless TB cases by year 4 3 sm neg sm pos
18 Define outbreak-related case Make a quick survey of known cases and the community situation Surveillance data Populations at risk Environmental factors agent host environment 18
19 Review of medical records Estimating Infectious Period 19
20 Estimating infectious periods Estimating infectious periods 2
21 Clinical Status- Index Case Lodging: Home Hostel Home Hospitalized at Facility: C C B B A Sputum TB Culture: Chest X-Ray: Normal +/- Progressive Noncavitary Pneumonia Cough: Absent cough Mild Moderate to Severe Cough Aug Sep Oct Nov Dec Jan Interview outbreak cases 21
22 Investigate environmental factors Figure 4 - Clustering of TB cases and Persons with LTBI at the Hostel Second Floor October 1 November 19, 21 Patient, TB infected Visitor, TB infected Index Case 22
23 Formulate a hypothesis/conduct investigation What is contributing to increase risk? Host factors contributing to the problem Environmental factors contributing to the problem Connect the dots - How are outbreak patients related? May lead to discovery of transmission sites and additional contacts 1999 Cases TB Case Location
24 Cases TB Case Location Cases TB Case Location
25 Cases TB Case Location Cases TB Case Location
26 Cases TB Case Location Cases TB Case Location 26
27 Conduct investigation: Prioritize Contacts for TB Evaluation Exposure risk Calculate relative risks of different exposure groups Host factors HIV or immunosuppressed children Find and screen contacts LTBI TST or IGRA (blood assay testing) TB Disease Symptom review Chest radiograph Pediatric cases HIV pos/immunosuppressed Sputum exam HIV testing 27
28 Analyze data Contact evaluation rate Contacts evaluated/contacts identified LTBI rate TB Disease rate Exposure risk categories Statistical analysis Test hypotheses Risk calculations P-values (<.5) Confidence intervals narrow, do not include 1 28
29 Outline of Jail POD F POD A Inmate B POD E POD B POD D POD C Inmate A GYM Prioritization for approx. 35 contacts (who were released from jail and did not want to be found!) Priority 1: Cell mate to either index case or a pod mate to case B in the 2 months prior to diagnosis. Priority 2: Pod mate to case B any other time Priority 3: Pod mate to case A or employee 29
30 Aggregated Report of Program Evaluation Analysis of outbreak investigation Priority 1 Priority 2 Priority 3 sought evaluated 58 62% 3 6% 54 28% TST positive 24 5% 4 14% 16 32% previous positive started treatment 25 74% 5 83% 11 55% completed 1 4% 2 4% 2 18% moved 1 lost 6 2 refused 1 still on 9 36% 2 4% 6 55% Employees only % 7 37% % 1 17% 2 3 5% Aggregated Report of Program Evaluation Analysis of outbreak investigation One's Two's Three's E mployees only sought evaluated % 5 3 6% % % TST positive 24 5% 4 14% 16 32% 7 37% previous positive started treatment % % % % completed 1 4% 2 4% 2 18% 1 17% moved lost refused still on 9 36% 2 4% 6 55% 3 5% 3
31 Aggregated Report of Program Evaluation Analysis of outbreak investigation One's Two's Three's Employees only sought evaluated 58 62% 3 6% 54 28% 2 31% TST positive 24 5% 4 14% 16 32% 7 37% previous positive started treatment 25 74% 5 83% 11 55% 6 75% completed 1 4% 2 4% 2 18% 1 17% moved 1 lost refused 1 still on 9 36% 2 4% 6 55% 3 5% Priority Sought Evaluated Relative risks LTBI (Latent TB infection) TBD suspect or case Relative Risk High 93 48(52%) 2(43%) 2 (4%) 3.63 (p<.1) Medium 51 25(49%) 4(16%) 1.27 (p>.5) Low* (65%) 12(11%) 31
32 Cas e 1 Cas e 2 H i g h Y e s C ellm ate H i g h Y e s to c as e N o L o w H i g h Y e s M e d Y e s Ce llm a te N o Pod m a te Afte r 7 /1/5 N o Po d m a te B efo re 7 /1/5 Oth er in m a te s & em p lo y ees L o w No * nitial te t re ult only Formulate conclusions Implement control measures Make report MMWRs Journals newsletter Evaluation of Contact Prioritization in a Rural Jail/TB Investigation Missouri, 25 Phillips L 1,2 Weiser T 1,2 Tremblay C 2 Fortune D 2 Talken R 2 1 Missouri Department of Health and Senior Services 2 Centers for Disease Control and Prevention I. Background: Contact investigation guidelines: For optimal efficiency, priorities should be assigned to contacts, and resources should be allocated to complete all investigative steps for high- and medium-priority contacts. MMWR December 16, 25/Vol.54/No.RR-15 II. The Outbreak: Two patients with TB disease (TBD) were diagnosed in the same month in a rural MO jail. There were 23 inmates in six pods in the 167- inmate capacity jail. There was no TB screening program in this jail, nor was there a computerized inmate log. III. Initial Screening at Time of Patient 1 s Diagnosis: Pod A B C Patient 1 D E Patient 2 IV. The Jail: No. Positive/ No. Tested 1/19 /5 1/19 3/14 8/17 Percent Positive 5% % 5% 21% 47% V. Patient 2 s CXR: VI. The Challenges: Patient 1 incarcerated 1 weeks + Patient 2 incarcerated 2 weeks = 321 discharged inmates to find for contact testing. We needed to prioritize these 321 discharged inmates plus 62 employees. They were prioritized high, medium and low based on characteristics of their disease, exposure, and results of initial TST results of currently incarcerated contacts. After the initial investigation, we needed to evaluate the prioritization scheme to assure that contacts were prioritized correctly and those most at risk were evaluated. VII. The Prioritization Scheme: VIII. The Results: Priority Sought High Medium Low* Evaluated 48(52%) 25(49%) 111(65%) * Initial test results only I s s Evaluated contacts # of contacts high medium low priority ranking not evaluated evaluated LTBI (Latent TB infection) 2(43%) 4(16%) 12(11%) Further anal ysis of the low priority group The low risk priority group included low risk inmates and all employees Low risk inmates: Employees Sought = 115 Sought = 62 Initially Initially Evaluated = 52 Evaluated = 62 (45%) (1%) TST+ = 6 (1%) TST+ = 8 (12%) TBD = TBD = TBD suspect or case 2 (4%) Relative Risk 3.63 (p<.1) 1.27 (p>.5) LTBI/TBD in Contacts # of contacts high medium low* priority ranking * Low pr iority inma te s i nitial TST results only not infected TB disease TST positi ve POD F POD E Patient 2 POD D GYM POD A POD B Patient 1 POD C IX. The Conclusions: By evaluating our prioritization scheme during the outbreak response, we showed that high priority contacts were over three times as likely to have a positive tuberculin skin test (TST). We successfully directed limited resources to contacts most at risk. Employees had a greater than expected rate of LTBI Airflow issues - Requested NIOSH assistance No routine TST screening program previous to this outbreak. Now: Binannual TSTs for 3 years or until no new conversions Inmate screening symptom screening for all at intake Inmates incarcerated > 2 weeks undergo TST testing UV lighting installed in the air handling system 32
33 Implement control measures Administrative controls Targeted testing Case finding surveillance Environmental controls Enhanced ventilation UV light intervention Personal protective equipment Isolation/masks Health professions education After action review Regroup and document what worked and what did not work All participants Lessons learned - implement change for the next investigation 33
34 New Orleans Bay St. Louis MS Florida Texas The recorded storm surge of 3 feet high in Bay St. Louis, MS was the highest ever recorded in U.S. history Hurricane Katrina 34
35 Return Route TB Control plan for Lake Charles and Western Louisiana Parishes post-hurricane Rita Set-up contingent reporting network format similar to Hurricane Katrina (if needed) 35
36 Lessons learned from Hurricane Katrina BK! October 25 Instructions to TB patients days before hurricane hit 3 days worth of meds given to all patients March 26 Result: All TB patients tracked and accounted for okay References Reichler, M. R., R. Reves, et al. (22). "Evaluation of investigations conducted to detect and prevent transmission of tuberculosis.[see comment]." JAMA 287(8): Buff AM (27) TB Outbreak Investigations in Low-Incidence Settings presentation from Identifying, Investigating, and Controlling TB and MDR TB Outbreaks presented at the International Union Against TB and Lung Disease (IUATLD) annual meeting in Cape Town South Africa, November 7, 27. CDC (28) Glossary of Epidemiological Terms retrieved on April 8, 28 from Gregg, MB (22) Field Epidemiology 2 nd Ed. Oxford Press University Press New York, NY p.9 Passannante, M. and N. Ahamed, Eds. (25). Basic Epidemiology for Program Staff, New Jersey Medical School National Tuberculosis Center. MODHSS. (27a). "Missouri Tuberculosis Information Summary " Retrieved April 8, 28, from Phillips L, Carlile J, Smith D (24). "Epidemiology of a tuberculosis outbreak in a rural Missouri high school." Pediatrics 113(6): e
37 References (2) Evaluation of contact prioritization in a rural jail tuberculosis investigation Missouri, 25 (poster) Phillips L, Weiser T, Tremblay C, Fortune D, Talken R American Thoracic Society International Conference, May 26 Malone J, Ijaz K, Lambert L, Rosencrans L, Phillips, L (24). "Investigation of healthcare-associated transmission of Mycobacterium tuberculosis among patients with malignancies at three hospitals and at a residential facility." Cancer 11(12): CDC (26) Tuberculosis Control Activities after Hurricane Katrina Morbidity and Mortality Weekly Report, March 31, 26 / 55(12);
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