TB Program and Epidemic aka B2B Nulda Beyers On behalf of DTTC BOD Workshop 30 September2013
Trend in tuberculosis incidence, selected countries in Africa 1400 1200 Rate per 100,000 1000 800 600 400 200 South Africa Zambia Malawi Mozambique Tanzania 0 1990 1995 2000 2005 2006 2007 2008 2009 Calendar year Estimates from the WHO Global Report
The Universe of TB Where are the missing cases? Global % All cases 100 Not accessing services Accessing services but not examined Diagnosed not treated (initial default) Treated in other sectors 7 15 3 10 Recorded unreported 4 Reported 61
Exit study - Aim To determine how many adults access healthcare facilities but are not diagnosed with TB, in facilities where TB diagnosis depends on passive case finding.
Exit study - results 4686 exits 665/4686 (14%) consented 1122/4686 (24%) on treatment or fetched meds 2899/4686 (62%) declined 423/665 (64%) symptomatic 242/665 (36%) asymptomatic
Exit study - results 423/665 (64%) symptomatic 36/423 (9%) accessed b/o chest complaints 387/423 (91%) did not access b/o chest complaints 3/36 (8%) were asked about chest complaints 13/387 (3%) were asked about chest complaints 1/3 (33%) was asked for sputum 3/13 (23%) were asked for sputum 1/1 gave a sputum and had return date 1/3 (33%) gave a sputum and had return date
Exit study - results 423 symptomatic 21/423 (5%) TB Cases 385/423 (91%) not TB Cases 17/477 (4%) missing data 0/21 accessed because of chest complaints 0/21 asked about chest complaints 0/21 asked to give a sputum
Exit study - conclusion Many patients with infectious TB access healthcare, but are not diagnosed. Intensified case finding must start within the facility. B2B
Initial Default (Initial Loss to Follow-up) 2004-2006 Stellenbosch District (9 fixed clinics, 4 mobile clinics) 64/369 (17%) TB suspects with 2 positive smears not on treatment Ravensmead and Uitsig 58/373 (16%) initial defaulters (2 smear+, or culture+): 24% died 45% not found (address!!) results often not available or not given to the patient culture result takes long time IJTLD 2008; 12(8):936-941 IJTLD 2008; 12(7):820-823
Initial Loss to Follow-up 5 other provinces (122 clinics) - 24% ILTF IJTLD 2013; 17(5): 603
Conslusion Many patients diagnosed with TB but do not start treatment B2B
Drug Resistant TB Clinical course of patients using routine data. To determine the progression from drug sensitive to drug resistant (MDR and XDR) by combining clinical and bacteriological data.
Drug Resistant TB Methods Database (routine TB register data) Sample bank Additional laboratory tests for Drug Resistance Home visits and follow up
Drug Resistant TB Retreatment after default Historical cohort 2,136 smear positive cases (1996-2008) - 291 were treated again for TB Re-treatment rate in defaulters compared to retreatment rate in successfully treated cases. 6.86 (95% CI: 5.59 8.41) per 100 PY after default 2.09 (95% CI: 1.81 2.41) per 100 PY after cure. 27.9% (95% CI: 22.8% 33.8%) of defaulters were treated again for smear-positive TB. PLoS One. 2012;7(9):e45724.
Evolution of Drug Resistant TB Retreatment after default 50% 45% Proportion with smear+ recurrence 40% 35% 30% 25% 20% 15% 10% 5% 0% 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Time since end of the previous episode (years) After treatment default, initial smear 3+ After treatment default, initial smear 1+ or 2+ After cure/completion, initial smear 3+ After cure/completion, initial smear 1+ or 2+ PLoS One. 2012;7(9):e45724.
Drug Resistant TB Default after previous treatment Same cohort (141 treatment defaulters) Default rates in new cases compared to default rate in previously treated (OR) 1.79 (95% CI 1.17-2.73) after previous treatment success 6.18 (95% CI 3.68-10.36) after previous default 9.72 (95% CI 3.07-30.78) after previous failure Int J Tuberc Lung Dis. 2012; 16(8):1059-1065
Drug Resistant TB Default after previous treatment Other risk factors: Male (P=0.008), Age 19-39 years (P=0.02) Positive sputum-smear (P=0.02) Int J Tuberc Lung Dis. 2012; 16(8):1059-1065
Drug Resistant TB Risk of developing MDR TB rpob mutant (MDR) present Total Number % P- value All cases 1,689 56 3.3 Number of previous episodes 0 1432 41 2.9 1 208 10 4.8 >1 49 5 10.2 <0.01
Drug Resistant TB Risk of developing MDR TB rpob mutant (MDR) present Category of episode Total Number % P- value New 1,137 24 2.1 After cure 80 2 2.5 After completion 334 18 5.4 After default 130 12 9.2 <0.01 Too few cases after failure or unknown for analysis
Drug Resistant TB Conclusion High rate of retreatment after default High rate of default after previous treatment High rate of MDR after retreatment, especially smear positive B2B
Amplification of MDR/XDR TB in children
Family One A1 A2 A3 Family One Uncle s mother Code 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 A1 Uncle A2 Index child A3 Death Treatment for drug susceptible TB Treatment for MDR TB Treatment for XDR TB TB with no treatment Emerg Infect Dis. 2012;18(8):1342-5
Family Two B3 B1 B4 B5 B2 Family Two Oldest brother B1 Sister B2 Mother B3 Other brother B4 Index child B5 Death Treatment for drug susceptible TB Treatment for MDR TB Treatment for XDR TB TB with no treatment Emerg Infect Dis. 2012;18(8):1342-5
Conclusion Amplification Potential for resistance to be both transmitted and amplified within families Contact management Diagnose and treat and prevent retreatment B2B
The Universe of TB Where are the missing cases?
Exit: Final Conclusion = B2B Many patients with infectious TB access healthcare, but are not diagnosed. Intensified case finding must start within the facility. Initial Loss to Follow-up Many people with infectious TB access health care and are diagnosed, but do not start treatment
Final Conclusion = B2B MDR and retreatment High rate of retreatment after default High rate of default after previous treatment High rate of MDR after retreatment, especially in S+ Diagnose and treat and prevent retreatment Resistance transmitted and amplified within families Contact management
Acknowledgements People in communities City of Cape Town Health Directorate Western Cape Government, Department of Health TREAT TB, USAID, Union