REDUCING ADULT MORTALITY WORLDWIDE: THE NEXT 40 YEARS Sources of support: ICMR and RGI (India); FIC, NIH (US); LKSKI, IDRC & CIHR (Canada); CTSU & MRC (UK) Prabhat Jha, on behalf of MDS Collaborators Prabhat.jha@utoronto.ca
Conclusions Control of selected infectious diseases will remain key (HIV, TB, Malaria) Tobacco control and widely practicable treatments will be key for chronic disease control The generation and diffusion of new knowledge and products is essential for 21 st century gains in health
Worldwide deaths, all causes: 60 M/year dying in early 2000s Age range Deaths per year 0-34 ~20M 35-69 ~20M (70+) (~20M) M = Million
130M/year now being born: future deaths among them (at current age-specific death rates) Age range Future deaths 0-34 ~20M 35-69 ~40M (70+) (~70M)
Malaria mortality rates in India are high in early childhood and in later middle age * Study-attributed Indian malaria mortality rates WHO indirect estimates of Indian malaria mortality rates Age-specific all-india malaria-attributed death rates estimated from the present study, and those estimated indirectly for WHO * No. of study deaths per age class (in red)
Malaria-attributed deaths: estimated Age range All India, 2005 Deaths (thousands) Death rate per 100 000 (lakh) <1 months 0 44 1-59 months 55 5-14 years 29 12 15-29 years 25 8 30-44 years 22 10 45-59 years 37 27 60-69 years 37 75 Subtotal, ages 0-69 years (lower, upper bounds) national totals, by age 205 (125, 277) 120 thousand at ages 15-69 70 + 71 236 18
Malaria deaths occurred where the most dangerous type (Plasmodium falciparum) of malaria parasite occurs
2.5% INDIA: HIV prevalence among young antenatal clinic attendees from 2000 to 2007 2.0% 1.5% 1.0% 0.5% all sites Low-HIV states; n=297 841 p trend =0.418 continous sites High-HIV states; n=354 567 p trend <0.0001 0.0% States Clinic 2000 2001 2002 2003 2004 2005 2006 2007 High-HIV All sites % 1.96 1.63 1.53 1.10 1.06 1.07 0.87 0.74 (99%CI) (1.57, 2.34) (1.33, 1.92) (1.27, 1.79) (0.99, 1.22) (0.96, 1.17) (0.96, 1.17) (0.78, 0.97) (0.65, 0.82) Continuous sites % 1.90 1.71 1.79 1.62 1.10 1.20 1.04 0.99 (99%CI) (1.45, 2.35) (1.29, 2.13) (1.38, 2.20) (1.21, 2.03) (0.77, 1.43) (0.85, 1.55) (0.72, 1.36) (0.68, 1.30) Low-HIV All sites % 0.32 0.21 0.33 0.25 0.27 0.28 0.25 0.23 (99%CI) (0.19, 0.46) (0.13, 0.29) (0.23, 0.42) (0.19, 0.31) (0.19, 0.35) (0.20, 0.37) (0.20, 0.30) (0.18, 0.28) Continuous sites % 0.31 0.26 0.36 0.38 0.32 0.12 0.26 0.20 (99%CI) (0.17, 0.45) (0.13, 0.39) (0.21, 0.51) (0.22, 0.54) (0.18, 0.46) (0.03, 0.27) (0.13, 0.39) (0.08, 0.31)
HIV-attributable deaths in India, 2004 age 15-59* High HIV states Low HIV states Men Women Total 78 5/868 0 9 0% (6 6-11 6) 21 3/2211 9 1 0% (0 1-2 5) 78 9/1821 9 4 3% (2 5-6 0) 20 7/1258 0 1 6% (0 1-3 8) 99 6/3079 9 3 2% (1 9-4 6) * 99% Confidence intervals Source: Jha et al, 2009
HIV infected adults age 15-49 in India, 3 methods Method/year Prevalence in % (99%CI) Mortality-based prevalence, 2004 HIV-testing, NHFS-3, 2005-6 0 26 (0 13-0 39) 0 28 (0 23-0 35) Survival-based, 2004 0 25 (0 15-0 33) M adults infected (99%CI)* 1 49 (0 75-2 19) 1 59 (1 31-1 99) 1 42 (0 85-1 90) * Official estimate is 2.3M (range 1.9-3.0M) Source: Jha et al, 2009
Worldwide, HIV, TOBACCO, ALCOHOL & OBESITY are the only big causes of death that have increased substantially since 1990 in some large populations, after allowing for population growth
Large apparent fluctuations in Russian vascular mortality may be due mainly to fluctuations in alcohol poisoning or alcoholic heart damage mis-certified as vascular disease Source: Zaridze, Peto et al, 2009, Lancet
Male mortality 1970-2010 Country 1970 1990 2010 Change Rank 2010 Russian Federation 31 32 41 34% 159 South Africa 42 38 53 28% 177 Brazil 27 24 19-29% 84 India 33 27 23-31% 106 China 24 20 15-35% 59 France 20 16 12-42% 34 Germany 19 16 10-47% 25 Switzerland 17 13 7-55% 5 US 23 17 13-43% 45 Canada 19 13 8-55% 11 Chile 29 19 12-61% 33 Korea (Rep) 38 23 11-71% 31 Source: IHME, 2010
Male rate 7.5 / 1000 (25% dead) Male Female rate 4.5 / 1000 (15% dead) Female Vascular death at ages 35-69, UK 2005: 7% Male, 3% Female
Changing vascular mortality: prevention & treatment Tobacco (smoker @ 3x non-smoker risk) Blood lipids* Blood pressure* Obesity * Secondary prevention: high annual risk 3 by long-term statin, BP lowering & aspirin
Treat high risk, not high BP or high cholesterol: Secondary prevention by combining 3 or 4 generic drugs in patients with some diagnosed vascular disease Aspirin vs not in patients with previous heart attack, angina, stroke: annual event rate 5% vs 7% BP lowering + aspirin vs aspirin 3% vs 5% Statin (cholesterol) + BP + aspirin vs BP + asp. 2% vs 3% 10-year risk: 50% untreated vs 16% for 3 drugs Source: Peto et al, 2006
Variations by SES: MI treatments in India Rich 1,078 (5.3) Upper middle 4,590 (22.5) Lowr middle 10,737 (52.6) Poor 3,999 (19.6) Thrmbly [STE] 309 (60.6) 1,610 (64.5) 4,092 (62.9) 1494 (52.3) Anti platelet 1,046 (97.0) 4,481 (97.6) 10,524 (98.0) 3,917 (97.9) Beta blockers 634 (58.8) 2,811 (61.2) 6,656 (62.0) 1,983 (49.6) Lipid lowerng 660 (61.2) 2,693 (58.7) 5,816 (54.2) 1,440 (36.0) ACEI/ARB 681 (63.2) 2,619 (57.1) 6,131 (57.1) 2,162 (54.1) Angio 441 (40.9) 1,636 (35.8) 2,310 (21.7) 341 (8.6) PCI 165 (15.3) 594 (13.0) 691 (6.5) 80 (2.0) CABG 81 (7.5) 226 (4.9) 257 (2.4) 27 (0.7) Any Re-vascl 83.4% 82.4% 71.8% 55.0% All p<0.0001 Denis Xavier et al, Lancet 2008;
Mortality by socio-economic strata Rich Upr mid Lowr mid Poor P Death rate (un-adj) 5.5 5.9 6.5 8.2 <0.0001 Death rate (adj-rfs) 5.1 1.0 5.9 1.16 (0.83,1.63) 6.7 1.32 (0.96, 1.82) 7.8 1.57 (1.12, 2.20) 0.0093 Death rate (adj-rf+trt) 6.9 1.0 7.0 1.01 (0.50, 2.02) 6.5 0.94 (0.48, 1.84) 6.7 0.96 (0.46, 2.01) 0.9487 RF, CF: age, sex, prev MI, DM, HTN, smoking, BP, HR, Killip, BMI Trtm: type of hospital, time to hosp, in-hospital drugs, interventions. Denis Xavier et al, Lancet 2008;
Male and female rates are on different scales
UK female cancer mortality trends at ages 35-69, 1950-2007: selected sites Main cause of trend in recent decades Breast: treatment Lung: cigarettes Colorectal: treatment Cervix: screening Stomach: Unknown
Leading causes of cancer mortality and disability Low and middle income countries, 2001 CAUSE Deaths DALYs in 000s in millions 1. Tracheas, bronchus, lung * 771 10.7 2. Stomach * + 696 9.6 3. Liver * + 505 7.9 4. Esophagus * 380 5.3 5. Colon and rectum 357 5.1 6. Breast 317 5.5 7. Mouth and oral * 271 4.1 8. Cervix + 218 3.8 ALL CANCERS 4,955 74.5 * Smoking a major cause + Chronic infection a major cause Source: Lopez et al, GBD, 2006; Parkin et al, 2006; DCP-2
A billion tobacco deaths in the 21 st century on current smoking patterns Source: Peto et al, 2006; Jha, 2009
INDIA: Years of life lost among 30 year old smokers * Men who smoke bidis Women who smoke bidis Men who smoke cigarettes 6 years 8 years 10 years * At current risks of death versus non-smokers, adjusted for age, alcohol use and education (note that currently, few females smoke cigarettes) Source: Jha et al, NEJM, Feb 2008
Deaths from smoking in year 2010 in India Age range Women Men Both Ages 30-69 93,000 579,000 672,000 All adults 20+ 128,000 807,000 935,000 Annual deaths from smoking will rise from 930,000 to 1,000,000 during 2010s Source: Jha et al, NEJM, Feb 2008
Low quit rates in India: prevalence of ex-smoking among males ages 45-59 in India, 2004 Ke rala 7.4 Assam 2.4 Madhya Pradesh 2.1 INDIA 2.0 Karnatak a 2.0 M aharas htra 2.0 Rajas than 1.9 Andhra Pradesh 1.8 Jammu & Kashmir 1.8 Himachal Pradesh 1.6 Gujarat 1.3 Punjab 1.2 West Bengal 1.2 Bihar 1.1 Uttar Pradesh 1.0 Delhi 0.9 Orissa 0.9 Tamil Nadu 0.9 Haryana 0.8 Source: Jha et al, forthcoming
China is the largest cigarette producer 2011-1-26 27
THE MILLION WOMEN STUDY (UK now: 7 years follow-up, 42,000 deaths) Dame Valerie Beral, U of Oxford, unpublished First large prospective study showing full effects of prolonged smoking in women Smokers had started at age ~19 years (mean ~15 cigarettes/day) Big risks, even though UK cigarette yields have been lowered in recent decades
THE MILLION WOMEN STUDY ALL-CAUSE MORTALITY Relative risk (95%CI) 5 4 3 2 1 0 0 5 10 15 20 25 30 Cigarettes/day
Source: Peto et al, 2000; Thun et al, 2003
THE MILLION WOMEN STUDY ALL-CAUSE MORTALITY in current & ex-smokers
Over 1.3 million (M) quitters in Canada, 1999-2009 age 15+ Year Ex-smoker Current Never 1999 6.1 M (50%) 2009 7.4 M (60%) 6.1 M (50%) 4.9 M (40%) 11.9 M (49%) 15.4 M (56%) Source: Jha et al, forthcoming
Smoking-attributable mortality in the lowest and the highest social strata Annual death rates per 1000 men aged 35 69 years 0 2 4 6 8 10 6.14 5.32 4.25 3.49 1986 1991 1996 2001 2.22 1.82 1.49 1.09 3.90 3.91 1990-96 1997-99 0.99 1.01 9.09 7.93 1995 2002 2.38 1.15 3.76 3.11 3.08 1991-94 1995-97 1998-2000 1.21 0.93 0.87 low high 4.60 4.37 4.37 1995-98 1999-2002 2003-2006 1.21 0.99 0.88 Canada France Poland Switzerland USA Source: Singhal, Jha et al, 2010
Life expectancy loss of 3 years with moderate obesity and 10 years with smoking Source: Peto, Whitlock, Jha, NEJM, March 2010
Knowledge, diffusion and institutions for control of adult mortality 1. R&D is central- gains in US were perhaps 10-20% of GDP in the past 3 decades 2. Count the dead: Only 20 M of 60 M deaths worldwide are certified medically 3. Enforce the Framework Convention on Tobacco Control 4. Need for large-scale clinical trials to create widelypracticable therapies, inc. global networks of research intensive universities 5. Partnerships to advance drug access (using infectious disease models, e.g. AmFRM) 6. A new TDR like program at WHO for chronic disease intervention research
Conclusions Control of selected infectious diseases will remain key (HIV, TB, Malaria) Tobacco control and widely practicable treatments will be key for chronic disease control The generation and diffusion of new knowledge and products is essential for 21 st century gains in health