Tuberculosis Transmission in Households and Communities
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1 Tuberculosis Transmission in Households and Communities Christopher C. Whalen, M.D., M.S. Department of Epidemiology and Biostatistics 2008, The University of Georgia. All rights reserved.
2 Model for M. Tuberculosis Transmission Partition transmission by social constructs Community Health Care Institutions Households Universe of M. tuberculosis Transmission
3 Model for M. Tuberculosis Transmission Assortment of susceptible individuals within social constructs Institutions Households Community
4 Kawempe Community Health Study Household Contact Study Kawempe Division, Kampala Uganda Research Aims Estimate household transmission M. tuberculosis infection Tuberculosis disease Stratify by HIV serostatus
5 Household Contact Study Design Index Cases Household Contacts Community Households Cure Relapse Death Baseline Evaluation Tuberculin Skin Testing Active Tuberculosis HIV Testing Baseline Evaluation Tuberculin Skin Testing Active Tuberculosis 3, 12, 24 Months TST Conversion Incident Tuberculosis Creates a cohort of household contacts exposed to an infectious index case
6 Effect of HIV Serostatus on TB Contact Characteristic HIV Serostatus of Index Case Seropositive (n = 249) Seronegative (n = 251) P Value n ( % ) No. contacts HIV seropositive 157 (16) 46 (5) Latent TB Infection 685 (71) 769 (80) Active TB 35 (3.6) 41 (4.3) NS HIV Serostatus of Contacts Seropositives (n = 203) Seronegatives (n = 1459) Latent TB Infection 151 (74) 1096 (75) NS
7 Percent Age-Specific Prevalence of TB Infection Household Contacts vs. Community Members Household Contacts Community Controls Risk Difference > 45 Whalen CC, et al. PLoS One, 2011 Age Groups (Years)
8 Secondary Attack Rates SAR TB SAR Infection Risk of TB after new Infection % Overall Age <= > HIV serostatus HIV HIV Whalen CC, et al. PLoS One, 2011
9 DNA Fingerprinting Household Contacts with Active TB HIV Status by HIV Sero-Status n RFLP Pattern Compared with Index Case Isolate Match No Match --- n (%) n (%) --- HIV negative (84) 6 (16) HIV positive (59) 9 (41) Total (75) 15 (25)
10 CART Analysis of MTB Transmission BMI > 20 (n = 12) HIV - (n = 7) HIV + (n = 5) RFLP Pattern Same Different HIV - (n = 30) Age 5 (n = 10) Age > 5 (n = 20) BMI 20 (n = 49) Age 5 (n = 5) 5 0 HIV + (n = 19) Age > 5 (n = 14) Care: No (n = 5) Care: Yes (n = 9)
11 TB Transmission in Community Cough Survey Rubaga Division, Kampala, Uganda, Random community sample Cough > 2 weeks -> sputum microscopy and culture Total Screened 5088 N % Total % Subgroup Chronic Cough Active TB HIV+ HIV Sekandi J, et al. Tuberculosis Prevalence in an Urban African City, in preparation
12 Percent Cases Active Case Finding for TB Rubaga Division, Kampala, Uganda P = ACF Active Case Finding PCF Passive Case Finding
13 Mathematical Model of TB Dynamics TB Epidemic driven by HIV seronegative TB cases when HIV prevalence is less than 30% Relative steady-state prevalence of tuberculosis according to HIV prevalence in population
14 TB Contact Networks Rubaga Division, Kampala, Uganda Network Size = 16 Density = 0.88 Degree mean = 13 Network Size = 15 Density = 0.34 Degree mean = 4
15 TB Contact Networks Kampala Uganda Local Bars Hospitals and clinics Connections between TB networks Partition contact networks by location and time Relate to TB infection and disease
16 Summary HIV seropositive index TB cases More frequent HIV+ contacts Possibly less infectious HIV seropositive contacts Similar likelihood for infection as other contacts Increased risk (3-fold) for disease HIV seropositive co-prevalent TB cases Different strains imply additional contact networks besides the household HIV seronegative TB cases appear to drive the TB epidemic until HIV prevalence is very high
17 Acknowledgements University of Georgia Andreas Handel Robert Kakaire Nibao Zheng Xiaoping Yin Case Western Reserve University Henry Boom Allan Chiunda Uganda Roy Mugerwa Moses Joloba Juliet Sekandi Sarah Zalwango Alphonse Okwera Henry Luzze Noah Kiwanuka Sponsors Tuberculosis Research Unit Fogarty International Center Doris Duke Charitable Foundation
18 Estimation of Secondary Attack Rates SAR D = SAR I * p D SAR D = Cases with same strain Total number of contacts SAR infection P H h P C c P H h P C c = ARI t SAR p D = SAR disease SAR infection
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20 Age 5 > 5 Latent TB Infection in Contacts (%) HIV + HIV Total 74 75
21 Replacement Principle As long as one case of tuberculosis is replaced by another, elimination of tuberculosis cannot be achieved
22 Replacement Principle of TB Control Interrupt Transmission Infectious Tuberculosis Index Case Prevent Relapse Tuberculosis Relapse Prevent Infection Prevent Disease Transmission of Active M. tuberculosis Tuberculosis In Contact Latent Tuberculosis Infection Active Tuberculosis In Contact Index Case Replaced
23 Platform for Global Public Health Action Comprehensive Plan for TB Elimination DOTS Treat LTBI Active Case Finding Environmental Controls Vaccination HIV Care Sustainable Development Poverty Mitigation Affordable Modern Housing Medical and Public Health Care Systems Competent TB Control Programs Scientific Research New Drugs New Vaccines New Diagnostics New Surveillance Stable and Supportive Government Commitment to TB Elimination Regional TB Control Alliances between Industrialized and Developing Countries
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