The epidemiology of tuberculosis Tuberculosis Workshop Shanghai, 12-22 May 28 Philippe Glaziou World Health Organization
Outline Epidemiology refresher Estimates of tuberculosis disease burden Notifications Progress in tuberculosis control Tuberculosis drug resistance TB-HIV will be presented separately
A model for TB epidemiology births uninfected primary TB latent TB primary TB infected: latent exogenous + endogenous TB deaths failure infectious TB relapse natural cure + drug cure treatment non-infectious TB relapse failure TB deaths failed recovered failed
TB incidence and prevalence rates incidence rate new TB cases = population!1 prevalence rate = existing TB cases population!1
Incidence, prevalence and disease duration Incidence (year 3) = 12 cases Prevalence in March of year 3 = 24 cases
Incidence, prevalence and disease duration Incidence (year 3) = 12 Prevalence in March of year 3 = 6
Important TB indicators Notification rate per 1, (all forms of TB, smear positive TB) Case detection rate = notifications / incidence Cure rate = % of smear positive cases finishing treatment and confirmed smear negative at the end of treatment TB case fatality rate = % deaths during TB treatment TB mortality rate = TB deaths / population
Estimating incidence, prevalence 1. incidence TB = 2. incidence TB = 3. incidence TB 4. incidence TB = and mortality notifications proportion detected prevalence duration = incidence infection! Styblo ratio deaths proportion cases dying (case fatality rate) Incidence, prevalence, deaths derived by rearranging 4 equations
Stop TB Strategy
Millennium Development Goals Implementation (DOTS) Indicator 24 (target year 25) Case detection 7% (> 6 m diagnosed) Treatment success 85% (> 5 m cured DOTS) Impact Indicator 23 (target year 215 cf 199) Prevalence 5% of 3/1K Deaths 5% of 3/1K (< 1m deaths) Stop TB Department
Outline Epidemiology refresher Estimates of tuberculosis disease burden Notifications Progress in tuberculosis control Tuberculosis drug resistance
Estimated numbers of new cases, 26 Estimated number of new TB cases (all forms) No estimate 999 1 9999 1 99 999 1 999 999 1 or more The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 26. All rights reserved
Estimated TB incidence rate, 26 Estimated new TB cases (all forms) per 1 population No estimate -24 25-49 5-99 1-299 3 or more The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 26. All rights reserved
Trends in estimated TB incidence rates (all forms, purple lines), and the annual change in incidence rates (red lines), for nine subregions and the world, 199 26 Incidence rate (per 1 /year) 4 3 2 1 High-income countries 1 5-5 -1 Change in incidence rate (% per year) Incidence rate (per 1 /year) 6 4 2 Central Europe 1 5-5 -1-15 Change in incidence rate (% per year) Incidence rate (per 1 /year) 9 6 3 Latin America 4 2-2 -4-6 Change in incidence rate (% per year) 199 1995 2 25-15 199 1995 2 25-2 199 1995 2 25-8 Incidence rate (per 1 /year) Incidence rate (per 1 /year) 21 18 15 12 9 6 3 12 9 6 3 Eastern Mediterranean 199 1995 2 25 Eastern Europe 199 1995 2 25 25 2 15 1 5-5 2 12 4-4 -12-2 Change in incidence rate (% per year) Change in incidence rate (% per year) Incidence rate (per 1 /year) Incidence rate (per 1 /year) 25 2 15 1 5 South- East Asia 199 1995 2 25 25 2 15 1 5 Africa - low HIV 199 1995 2 25 1.5 -.5 25 2 15 1 5-5 -1 Change in incidence rate (% per year) Change in incidence rate (% per year) Incidence rate (per 1 /year) Incidence rate (per 1 /year) 15 1 5 4 3 2 1 5 Western Pacific 199 1995 2 25 Africa - high HIV 199 1995 2 25 2-2 -4 2 15 1 5-5 Change in incidence rate (% per year) Change in incidence rate (% per year)
Frequency distribution of estimated changes in the TB incidence rate for 134 countries in 6 subregions, 1997 26 25 2 15 SEARWPR LAC EMR High income C&EEUR AFR 1 5-1 -8-6 -4-2 2 4 6 8 1
Correlates of the average annual change in TB incidence rate (vertical axes, %/yr), 1997 26, in different subregions of the world 1 8 6 4 2-2 -4-6 -8-1 (a) Latin America R 2 =.415 1 2 3 Percent adults infected with HIV (b) High-income countries 4 r 2 =.44-4 -8-12 2 4 6 8 Percent of TB cases foreign born 12 8 4 (c) Central and Eastern Europe r 2 =.66 4 (d) Eastern Mediterranean r 2 =.53-4 -4-8 -12 1 1 1 1 Health expenditure per capita ($PPP) -8-12 2 4 6 8 1 12 Health expenditure as percentage of GDP (e) Sub-Saharan Africa (f) Central and Eastern Europe 12 12 8 r 2 =.49 8 4 r 2 =.67 4-4 -8-4 1 1 1-12 1 2 3
Estimated global prevalence, mortality and incidence rates, 199 26 3 28 26 24 22 Prevalence 33 2 199 1995 2 25 14 31 135 29 27 25 Mortality 13 125 Incidence 23 199 1995 2 25 12 199 1995 2 25
Estimated TB prevalence (a) and death rates (b), by WHO region, for the MDG baseline year 199 and for 26, compared with the MDG target for 215 and with prevalence and death rates projected for 215 based on current trends (a) TB prevalence rate per 1 population (b) TB death rate per 1 population 6 1 5 8 4 6 3 4 2 1 2 AFR AMR EMR EUR SEAR WPR World AFR AMR EMR EUR SEAR WPR World 199 26 215 (current trends) MDG target 199 26 215 (current trends) MDG target
Outline Epidemiology refresher Estimates of tuberculosis disease burden Notifications Progress in tuberculosis control Tuberculosis drug resistance
Tuberculosis notification rates, 26 Notified TB cases (new and relapse) per 1 population No report 24 25 49 5 99 1 or more The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 26. All rights reserved
Progress towards the 7% case detection target (a) Case detection rate, smear-positive cases (%) 8 7 6 5 4 3 2 1 WHO target 7% DOTS begins 199 1995 2 25 21 215 Year average rate of progress 1995 2 (a) Open circles mark the number of new smear-positive cases notified under DOTS 1995 26, expressed as a percentage of estimated new cases in each year. The solid line through these points indicates the average annual increment from 1995 to 2 of about 134 new cases, compared to the average increment from 2 to 26 of about 242 cases. Closed circles show the total number of smear-positive cases notified (DOTS and non-dots) as a percentage of estimated cases.
Smear-positive case detection rate by DOTS programmes, by WHO region, 1995 26 8 7 6 5 4 3 2 AFR AMR EMR EUR SEAR WPR Global 1 1995 1996 1997 1998 1999 2 21 22 23 24 25 26
Outline Epidemiology refresher Estimates of tuberculosis disease burden Notifications Progress in tuberculosis control Tuberculosis drug resistance
Number of countries implementing DOTS (out of a total of 212 countries), 1991-26 2 18 184 Number of countries 16 14 12 1 8 6 4 2 1991 1992 1993 1994 1995 1996 1997 1998 1999 2 21 22 23 24 25 26
DOTS coverage by WHO region, 26 1 73 64 13 292 7.5 5.6 8 6 4 71 835 531 595 1714 1759 2 AFR AMR EMR EUR SEAR WPR The shaded portion of each bar shows the DOTS coverage as a percent of the population. The numbers in each bar show the population (in millions) within (dark portion) or outside (light portion) DOTS areas"
Treatment outcomes for HIV-positive and HIVnegative TB patients, 25 cohort The numbers under the bars are the numbers of patients included in the cohort 1 8 6 4 Not evaluated Transferred Defaulted Failed Died Com pleted Cured 2 HIV+ Smear-positive (6113) HIV- (14857) Smear-negative HIV+ (81) and HIV- extrapulmonary (132984) HIV+ (2577) Re-treatment HIV- (34863) (data from 47 countries) (data from 42 countries) (data from 25 countries)
Outcomes for those patients not successfully treated, by WHO region, 25 cohort DOTS Non - DOTS AFR AFR AMR AMR EMR EMR EUR EUR SEAR WPR SEAR WPR 82 1 2 3 4 1 2 3 4 Died Failed Defaulted Transfered Not evaluated
1 DOTS progress in high-burden countries, 25-26 9 China Cambodia Bangladesh Indonesia Viet Nam Afghanistan Philippines Target zone Treatment success (%) 8 7 6 Nigeria Pakistan DR India Congo Ethiopia UR Tanzania Kenya Mozambique Brazil Thailand Uganda South Africa Russian Federation Myanmar 5 4 2 4 6 8 1 12 DOTS case detection rate (new smear-positive, %)
Engagement of different types of providers in referral of TB suspects, high-burden countries, 26 Public general hospitals Medical college hospitals Military health-care facilities Prison health-care facilities NGO/mission clinics and hospitals Health facilities governed by health-insurance agencies Corporate health-care services Private hospitals Private practitioners 5 1 15 2 25 Number of countries
Engagement of different types of providers in free-of-charge TB treatment with recommended drugs, high-burden countries, 26 Public general hospitals Medical college hospitals Military health-care facilities Prison health-care facilities NGO/mission clinics and hospitals Health facilities governed by health-insurance agencies Corporate health-care services Private hospitals Private practitioners 5 1 15 2 25 Number of countries
Outline Epidemiology refresher Estimates of tuberculosis disease burden Notifications Progress in tuberculosis control Tuberculosis drug resistance
5 in Western Pacific 11 Europe 5 Americas 2 in South East Asia Coordinating Centre SRL Under evaluation 2 in African region 1 Eastern Mediterranean
MDR-TB among all TB cases 1994-27 * Sub-national averages applied to China, Russia, Indonesia. < 6% 6-2 % 2-4% >4% No data The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 26. All rights reserved
MDR estimates among new TB cases by country MDR (%) 1 2 3 4 5 6 WPR SEA EUR EMR AMR AFR Vertical segments represent 95% confidence intervals of country estimates; The horizontal lines show the global estimate with confidence bounds (dashed lines).
MDR (%) 2 4 6 8 1 MDR among retreatment TB cases by country WPR SEA EUR EMR AMR AFR Vertical segments represent 95% confidence intervals of country estimates; The horizontal lines show the global estimate with confidence bounds (dashed lines).
MDR-TB among all TB cases.4.3.2.1 P =.131. 1994 1996 1998 2 22 24 26 TB notification rate 2 18 16 14 12 1 8 6 4 2 1995 1997 1999 21 23 25.15 Any INH resistance among all TB cases Hong Kong SAR 1995-25.1.5 p=.4. 1994 1996 1998 2 22 24 26
7.35.35 6 5 4 3 2 1 Estonia 1997 1999 21 23 25 27.3.3.25.25.2.2.15.15.1.1.5.5.. p=.6213 p=.621 1997 1999 21 1997 1999 23 21 25 23 25 1 9 8 7 6 5 4 3 Latvia.35.3.25.2.15.1 2 1.5 p=.326. 1997 1999 21 23 25 27 1997 1999 21 23 25 1 9 8 7 6 5 4 3 2 Lithuania 1 1997 1999 21 23 25.35.3.25.2.15.1.5 p=.169. 1997 1999 21 23 25 notification rate % MDR among new
.7.6.5.4.3.2.1. % MDR-TB among new cases 1995 1997 1999 21 23 25 27 2 18 16 14 12 1 8 6 4 2 TB notification rate 1994 1996 1998 2 22 24 26.7.6.5.4.3.2.1 % Any INH resistance among new cases Peru 1996-25. 1995 1997 1999 21 23 25 27
.5.4.3.2.1. % MDR-TB among new cases p=.22 1993 1995 1997 1999 21 23 25 2 TB notification rate 18 16 14 12 1 8 6 4 2 1993 1995 1997 1999 21 23 25 27.15 % Any INH resistance among new cases Korea 1994-25.1.5. p=.12 1993 1995 1997 1999 21 23 25
% XDR-TB among MDR * Sub-national averages applied to Russia!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! < 3% or less than 2 cases in a survey 3-1% > 1% Report of at least one case No data The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 26. All rights reserved
Notified cases of MDR-TB (24 26) and projected patients to be treated (27 28) 5 non-glc 47 46 4 3 2 GLC Global plan target for number of MDR-TB patients to be enrolled on treatment: 26: 14 thousand 27: 52 thousand 28: 98 thousand 18 18 23 1 24 (11, 25%) 25 (16, 48%) 26 (18, 78%) 27 (112, 8%) 28 (116, 86%)
MDR-TB treatment outcomes in seven countries, 23 cohort 1 8 6 4 2 Germany (94) Lithuania (31) Brazil (316) Estonia (16) Latvia (165) Romania (585) Peru (158) Cured Completed Died Failed Defaulted Transferred Not evaluated
Global burden of MDR-TB 26 estimates of MDR-TB 489,139 incident cases 95% CI [455, 615,] 4.8% 95% CI [4.6% 6%] of all TB cases notified in 26
In conclusion, there were in 26 9.2 million new TB cases 1.7 million deaths from TB 14 million prevalent TB cases.5 million new MDR-TB cases Slow progress in case detection Decline in TB disease burden Challenge of HIV-TB and MDR-TB