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Combating Infectious Diseases and the Disease Control Priorities Project: A Convergence of Epidemiology

Combating Infectious Diseases and the Disease Control Priorities Project: A Convergence of Epidemiology, Economics and Research. Joel G. Breman, MD, DTPH Fogarty International Center National Institutes of Health. World Bank Washington, D.C. November 8, 2006. Outline.

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Combating Infectious Diseases and the Disease Control Priorities Project: A Convergence of Epidemiology

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  1. Combating Infectious Diseases and the Disease Control Priorities Project: A Convergence of Epidemiology, Economics and Research Joel G. Breman, MD, DTPH Fogarty International Center National Institutes of Health World Bank Washington, D.C. November 8, 2006

  2. Outline • DCPP Objectives • Burdens - Global - Infectious Diseases • Malaria Case Study • Intervention Cost-Effectiveness - Best Buys - One Million Dollars • Main Messages

  3. Objectives of DCPP (1) To decrease illness, disability, death, and economic burden by: • Developing an evidence base to inform decision-making by: • Providing estimates of the cost-effectiveness and impact of single interventions and packages • Collaborating in defining disease burdens globally and regionally • Summarizing implementation experience in different regions and globally www.dcp2.org

  4. Objectives of DCPP (2) • Communicating major findings • “Best buys” and the “worst buys” • Disseminating the results • Stimulating national priority setting and program implementation www.dcp2.org

  5. Disease Burdens • Deaths • Disability-Adjusted Life Years • Global • Infectious Diseases

  6. High Income (% total deaths) (n =7.89 million (14%) Ischemic heart disease (17.3) Cerebrovascular disease (9.9) Trachea, bronchus, lung cancer (5.8) Lower respiratory infections (4.4) Chronic obstructive pulmonary disease (3.8) LMICs (% total deaths) (n = 48.35 million (86%) Ischemic heart disease (11.8) Cerebrovascular disease (9.5) Lower respiratory infections (7.0) HIV/AIDS (5.3) Perinatal conditions (5.1) Leading Causes of Death in High and Low-/Middle-Income Countries (LMICs), 2001 (Total = 56.24 million) Mathers et al., 2006, in Lopez et al, Global Burden of Disease and Risk Factors

  7. High Income (% total deaths) (n = 7.89 million (14%) Colon and rectum cancers (3.3) Alzheimer’s and other dementias (2.6) Diabetes mellitus (2.6) Breast cancer (2.0) Stomach cancer (1.9) Total: 53.6% (ID = 4.4%) LMICs (% total deaths) (n = 48.35 million (86%) Chronic obstructive pulmonary disease (4.9) Diarrheal diseases (3.7) Tuberculosis (3.3) Malaria (2.5) Road traffic accidents (2.2) Total: 55.3% (ID = 21.8%) Leading Causes of Death in High and Low-/Middle-Income Countries (LMICs), 2001 Mathers et al., 2006, in Lopez et al, Global Burden of Disease and Risk Factors

  8. Disability-Adjusted Life Years (DALYS)Burden of Disease on a Defined Population • Aggregate of premature mortality, morbidity, and disability • Adjustments made for • life expectancy • long-term disability (weighted) • Valid indicator of population health • Tied to effectiveness of interventions

  9. Disease Burden by Income, 2001 Disability-Adjusted Life Years (DALYs) For infectious For all diseases, no. Infectious diseases burden (%)* and parasitic Population in diseases, no. in Countries in millions (%) millions (%) millions (%) Low- and Middle-Income 5,219 (85) 1,387 (90) 321 (99) 29 High Income 929 (15) 149 (10) 3 (1) 4 324 (100) Total 6,148 (100) 27 1,536 (100) *includes respiratory infections Mathers et al, 2006, in Lopez et al, Global Burden of Disease and Risk Factors

  10. Leading Causes of Disability-Adjusted Life Years (DALYs), Globally, 2001(n = 1.54 billion) Cause% total • Perinatal conditions 5.9 • Lower respiratory infection 5.6 • Ischemic heart disease 5.5 • Cerebrovascular disease 4.7 • HIV/AIDS 4.7 • Diarrheal diseases 3.9 • Unipolar depressive disorders 3.4 • Malaria 2.6 • Chronic obstructive pulmonary disease 2.5 • Tuberculosis 2.3 Total (ID= 19.1%) 41.1 Mathers et al, 2006 in Lopez et al, Global Burden of Disease and Risk Factors

  11. Disease Burden, Low and Middle Income Countries, by World Bank Region, 2001 Disability-Adjusted Life Years (DALYs) Infectious diseases burden in region,%* For infectious For all diseases, and parasitic no. in millions Population in diseases, no. in millions (%) Region millions (%) (%) Sub-Saharan Africa 668 (13) 345 (25) 173 (54) 59 South Asia 1,388 (27) 409 (29) 88 (27) 31 Middle East/North Africa 310 (6) 66 (5) 7 (2) 16 1,850 (35) 346 (25) 37 (12) 14 East Asia/Pacific 526 (10) 104 (8) 10 (3) 13 Latin America/Caribbean Europe/Central Asia 477 (9) 117 (8) 5 (2) 6 29 Total 5,219 (100) 1,387 (100) 320 (100) *includes respiratory infections Mathers et al, 2006, in Lopez et al, Global Burden of Disease and Risk Factors

  12. Infectious Burden, Low- and Middle-Income Countries, by World Bank Region, 2001 Disease burden by region, % Disease Burden In LMICs Disease DALYs, % EA/P E/CA SA SSA ME/NA LA/C Respiratory inf. 6.3 36 40 4 14 4 3 HIV/AIDS 5.1 79 10 1 4 3 1 Diarrheal disease 4.2 37 38 4 15 4 1 Malaria2.9 89 6 2 3 1 .1 TB 2.6 22 38 2 30 3 4 Measles 1.7 59 28 2 10 0 1 STD 0.740 39 4 9 5 2 23.5 SSA = Sub Saharan Africa; SA = South Asia; ME/NA = Middle East/North Africa; EA/P = East Asia/Pacific; LA/C = Latin America/Caribbean; E/CA = Europe/Central Asia Mathers et al, 2006, in Lopez et al, Global Burden of Disease and Risk Factors

  13. Total DALYs% HIV/AIDS 17.8 Malaria 10.3 Lower respiratory infections8.4 Perinatal conditions 6.3 Diarrheal diseases6.1 Measles 4.6 Tuberculosis 2.4 Whooping cough 1.9 Road traffic accidents 1.8 Protein-energy malnutrition 1.6 Total61.2 (ID=56.5%) Leading Causes of Disability-Adjusted Life Years (DALYs) in Sub-Saharan African Region, 2001 Mathers et al. in Global Burden of Disease and Risk Factors, 2006

  14. Malaria • Manifestations • Burden • Interventions

  15. Manifestations of the Malaria Burden Anemia Long-term sequelae Hypoglycemia Acute febrile illness Severe illness Respiratory distress Death Hypovolemia Infected Mosquito Cerebral malaria Anemia Chronic effects Impaired growth and development Neurologic Cognitive Infected Human Malnutrition Developmental Low birth weight Abortion, stillbirth Infant and fetal mortality Fetus Pregnancy Acute illness Long-term sequelae Maternal Anemia

  16. Deaths from Malaria: Children Under Fiveand Total, Africa 2001 Number of malaria deaths Cause of malaria-related death • Under fives Cerebral malaria 110,000 Severe anemia 190,000-974,000 Respiratorydistress 110,000 Hypoglycemia 153,000-267,000 Low birth weight 62,000-363,000 Total deaths from malaria 625,000-1,824,000 962,000-2,806,000 • Total, all ages* Sources Breman, Alilio and Mills, 2004; Murphy and Breman, 2001 *Children under 5 represent 65 percent of all deaths in Africa as per Snow and others (2003).

  17. Under-Five Deaths from AIDS, Malaria, and Other Causes, per Thousand Births, 1990 and 2001, Sub-Saharan Africa Source: Lopez, Begg, and Bos 2006.

  18. Rate of Progress in Reducing Under-Five Mortality, 1960-2000: China, India, Latin America, and Sub-Saharan Africa Source: World Bank 2004 (CD-ROM version).

  19. Plasmodium falciparum in 2002Clinical Cases Snow et al, Nature 2005

  20. Acute Febrile Episodes and Malaria-Associated Febrile Episodes in African Children 0-4 years Living in Endemic Areas, 1995-2020 2000 1800 1600 1400 1200 1000 800 600 400 200 0 1919 960 Febrile Illness Millions 846 Malaria 400 423 188 1995 population: total 585 million, 521 million (89%) in malarious areas; children <5 years 104 million, 94 million in malarious areas; assume <5 year population grows ~ 3.2% per year and will double by 2018 2020 1995 J. Breman, AJTMH, 2001

  21. Control of the Malaria Burden Current Interventions Drugs (treatment, prevention) Insecticides (house spraying, larvicides) Environmental and Behavioral Modification Vaccines (preerythrocytic, blood stage, transmission-blocking) Genetic modification of vectors Future Interventions Protection (insecticide-impregnated materials)

  22. Cost-Effectiveness of Interventions Against Malaria in Sub-Saharan Africa Intermittent preventive treatment/ pregnancy (SP) Insecticide residual spraying Insecticide-treated bed nets Intermittent preventive treatment in pregnancy with drug switch 0 5 10 15 20 25 30 Cost-effectiveness ratio ($ per DALY averted) R. Laxminarayan et al (DCPP authors), 2006 in Disease Control Priorities in Developing Countries

  23. Table 21.6. CERs for ITNs, IRS, and IPT

  24. Table 21.6. CERs for ITNs, IRS, and IPT (2)

  25. Incremental Cost-Effectiveness Ratio of an Intervention CostsB – CostsA Effectiveness B – EffectivenessA • Interventions studied: • personal = 204 • population = 115

  26. Cost-Effectiveness of Interventions Against HIV/AIDS in Sub-Saharan Africa Antiretroviral treatment Home care Mother/child prevention Tuberculosis coinfection prevention/treatment Blood/needle safety Condom promotion/distribution STI diagnosis/treatment Voluntary counseling/testing HIV/AIDS - peer programs 0 200 400 600 800 1,000 1,200 1,400 1,600 Cost-effectiveness ratio ($ per DALY averted) Laxminarayan et al (DCPP authors), 2006, in Jamison et al, Disease Control Priorities in Developing Countries

  27. Tuberculosis

  28. The Neglected Tropical Diseases: Humanity’s Ancient Diseases of Stigma and Poverty • 13 Parasitic and Bacterial Infections • Rural Areas of Low-Income Countries • Poverty-Promoting Conditions • Child Development & Education • Pregnancy • Worker Productivity • Burdened humanity for centuries • “The Biblical Diseases” • Disabling and deforming • Associated with intense stigma Leprosy Lymphatic Filariasis Guinea Worm River Blindness

  29. Ranking of Communicable Diseases By DALYs Disease ConditionDisease Burden HIV-AIDS 84.5 million Neglected Tropical Diseases 56.6 million Malaria 46.5 million Tuberculosis 34.7 million Hotez PJ, Molyneux DH, Fenwick A, Ottesen E, Ehrlich Sachs S, Sachs JD PLoS Medicine 2006; 3: e102

  30. Cost-Effectiveness ofInterventions Related to Low-Burden Diseases in LMICs; Helminths, Leishmaniasis, Onchocerciasis, Trachoma Trachoma: drug treatments Trachoma: trichiasis surgery Onchocerciasis: Ivermectin Leishmaniasis: case finding and treatment Soil-transmitted helminths: Albendazole 1 10 100 1,000 10,000 Cost-effectiveness ratio ($ per DALY averted) Source: DCPP Authors

  31. “Best Buys”Neglected Opportunities

  32. “Best Buys”Neglected Opportunities in Sub-Saharan Africa (SSA) and South Asia (SA) (1) Laxminarayan et al (DCPP authors), 2006, in Jamison et al, Disease Control Priorities in Developing Countries

  33. Higher Cost Buys

  34. Perspective: Cost-Effectiveness and Coverage Neglected Cost-effective opportunities interventions High used widely Cost Effectiveness Interventions for Interventions to Low which scaling up scale back is inefficient Low High Current Coverage Laxminarayan et al, 2006, in Jamison et al, Disease Control Priorities in Developing Countries, 2nd ed.

  35. Perspective: Cost-Effectiveness and Coverage Malaria Leishmaniasis drugs, insecticide treatment treated nets High Cost Effectiveness Parkinson’s disease HIV/AIDS poor treatment adherence (programs) Low deep brain stimulation Low High Avertable Burden of Disease Laxminarayan et al, 2006, in Jamison et al, Disease Control Priorities in Developing Countries, 2nd ed.

  36. A Million Dollars Invested

  37. Service or Intervention Reducing under-5 mortality Expanding immunization coverage (EPI diseases) Switch to artemisinin-combination therapy (ACT) where malaria is drug-resistant Improved neonatal care (newborn resuscitation) Adding vaccines to EPI (Hib and hepatitis B) DALYs Averted ($ per DALY) 50,000-500,000 ($2-20) 50,000-125,000 ($8-20) 2,500-100,000 ($10-400) 4,000-24,000 ($40-250) How Much Health Will a Million Dollars Buy?

  38. Research and Product Development

  39. Share of Disease Burden Averted with Existing, Improved or New Interventions Not avertable, research needed Avertable with current interventions and coverage Avertable if cost-effective interventions applied more widely Avertable only with interventions that are less cost-effective b c a Effective coverage 0 Source: WHO, 1996. Investing in Health Research and Development

  40. Research, Training, and Support Needs According to Understanding of Diseases and Efficacy of Control Methods High High Training Efficacy of Control Methods Research Needs Low Low Some Moderate High Research Support Needs

  41. Research, Training, and Support Needs According to Understanding of Diseases and Efficacy of Control Methods High High Training Malaria Dengue HIV/AIDS Influenza Tuberculosis Cancers Alzheimers Efficacy of Control Methods SmallpoxGuinea wormPoliomyelitisH. influenzae type BMeaslesTetanus Research Needs Onchocerciasis Diarrheal diseases Low Low Some Moderate High Research Support Needs

  42. Expected Results of R&D New basic knowledge • Mechanisms of disease • Epidemiology and risk factors • Disease modeling and surveillance New and improved tools • Drugs • Vaccines • Diagnostics • Devices • Prostheses and equipment • Vector control • Environmental modification • Behavioral, social, and economic change

  43. Expected Results of R&D (2) New and improved intervention methods • Treatment algorithms and guidelines • Intervention packaging • Costing and cost-effectiveness • Delivery: health systems and health services

  44. Disease Burden and Research and Development Funding Malaria and R&D Alliance: Science, 13 January 2006: *Disability-Adjusted Life Year. DCPP estimates in millions are: cardiovascular = 208.8; HIV = 71.5; malaria = 40.0; tuberculosis = 36.1; Diabetes = 20.0; dengue = 0.5

  45. Main Messages[Better data are needed]

  46. Main Messages • 1. Unfinished infectious diseases agenda. • IDs predominate in Sub-Saharan Africa and South Asia • Children under five years suffer preventable IDs in all regions • All countries have vulnerable groups (immunodepressed, metabolic disorders, aged)

  47. The Age Distribution of Deaths Under Age-5, Low- and Middle-Income Countries, 2001 Total deaths, including stillbirths = 13.758 million 30% 28% 25% 25% 24% 23% 20% Percent distribution of deaths under Age-5 15% 10% 5% 0% Stillbirths Neonatal deaths Post-neonatal infant deaths Child deaths (aged 1 to (aged 28 days to 1 year) less than 5 years) Age category D. T. Jamison, et al, 2006 in Global Burden of Disease and Risk Factors

  48. Main Messages • 2. Three critical ID challenges are facing developing countries and the world: • Preventable levels of mortality and disability from malaria, TB, diarrhea, and pneumonia. • Unchecked HIV/AIDS pandemic. • Emerging Infections – Infectious causes of “non-communicable diseases”. – Be prepared for an influenza pandemic due to a novel virus, and other perils.

  49. Source: Dr. Anthony Fauci, 2005

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