combating infectious diseases and the disease control priorities project: a convergence of...
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Combating Infectious Diseases and the Disease Control Priorities Project: A Convergence of Epidemiology, Economics and
Research
World BankWashington, D.C.
November 8, 2006
Joel G. Breman, MD, DTPHFogarty International CenterNational Institutes of Health
Outline DCPP Objectives
Burdens - Global
- Infectious Diseases
Malaria Case Study
Intervention Cost-Effectiveness- Best Buys- One Million Dollars
Main Messages
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
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
Disease Burdens
Deaths
Disability-Adjusted Life Years
Global
Infectious Diseases
Leading Causes of Death in High and Low-/Middle-Income Countries (LMICs), 2001
(Total = 56.24 million)High Income (% total deaths)
(n =7.89 million (14%)
1. Ischemic heart disease (17.3)
2. Cerebrovascular disease (9.9)
3. Trachea, bronchus, lung cancer (5.8)
4. Lower respiratory infections (4.4)
5. Chronic obstructive pulmonary disease (3.8)
LMICs (% total deaths)(n = 48.35 million (86%)
1. Ischemic heart disease (11.8)
2. Cerebrovascular disease (9.5)
3. Lower respiratory infections (7.0)
4. HIV/AIDS (5.3) 5. Perinatal conditions (5.1)
Mathers et al., 2006, in Lopez et al, Global Burden of Disease and Risk Factors
High Income (% total deaths)(n = 7.89 million (14%)
6. Colon and rectum cancers (3.3)
7. Alzheimer’s and other dementias (2.6)
8. Diabetes mellitus (2.6)9. Breast cancer (2.0)10. Stomach cancer (1.9)
Total: 53.6% (ID = 4.4%)
LMICs (% total deaths)(n = 48.35 million (86%)
6. Chronic obstructive pulmonary disease (4.9)
7. Diarrheal diseases (3.7)8. Tuberculosis (3.3)9. Malaria (2.5)10. Road traffic accidents
(2.2)
Total: 55.3% (ID = 21.8%)Mathers et al., 2006, in Lopez et al, Global Burden of Disease and Risk Factors
Leading Causes of Death in High and Low-/Middle-Income Countries (LMICs), 2001
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
Disease Burden by Income, 2001
Mathers et al, 2006, in Lopez et al, Global Burden of Disease and Risk Factors
CountriesPopulation in millions (%)
For all diseases, no. in millions (%)
For infectious and parasitic diseases, no. in millions (%)
Infectious diseases
burden (%)*
Low- andMiddle-Income
5,219 (85) 1,387 (90) 321 (99) 29
High Income 929 (15) 149 (10) 3 (1) 4
Total 6,148 (100)
1,536 (100)
324 (100)
27
Disability-Adjusted Life Years (DALYs)
*includes respiratory infections
Leading Causes of Disability-Adjusted Life Years (DALYs), Globally, 2001
(n = 1.54 billion)Cause % total1. Perinatal conditions 5.92. Lower respiratory infection 5.63. Ischemic heart disease 5.54. Cerebrovascular disease 4.75. HIV/AIDS 4.76. Diarrheal diseases 3.97. Unipolar depressive disorders 3.48. Malaria 2.69. Chronic obstructive pulmonary disease 2.510. Tuberculosis 2.3Total (ID= 19.1%) 41.1
Mathers et al, 2006 in Lopez et al, Global Burden of Disease and Risk Factors
Disease Burden, Low and Middle Income Countries,
by World Bank Region, 2001
Disability-Adjusted Life Years (DALYs)
Region Population in
millions (%)
For all diseases, no. in millions
(%)
For infectious and parasitic diseases, no. in millions (%)
Infectious diseases
burden in region,%*
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 East Asia/Pacific
1,850 (35) 346 (25) 37 (12) 14
Latin America/Caribbean 526 (10) 104 (8) 10 (3) 13
Europe/Central Asia 477 (9) 117 (8) 5 (2) 6
Total
5,219 (100)
1,387 (100) 320 (100) 29
Mathers et al, 2006, in Lopez et al, Global Burden of Disease and Risk Factors
*includes respiratory infections
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
Disease burden by region, %
Disease
Disease BurdenIn LMICsDALYs, % SSA SA ME/NA EA/P
LA/C E/CA
Respiratory inf. 6.3 36 40 4 14 4 3
Malaria 2.9 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 0.7 40 39 4 9 5 2
Diarrheal disease 4.2 37 38 4 15 4 1
Infectious Burden, Low- and Middle-Income Countries,
by World Bank Region, 2001
HIV/AIDS 5.1 79 10 1 4 3 1
23.5
Leading Causes of Disability-Adjusted Life Years (DALYs) in Sub-Saharan African
Region, 2001Total DALYs %
1. HIV/AIDS 17.82. Malaria 10.33. Lower respiratory infections 8.4 4. Perinatal conditions 6.35. Diarrheal diseases 6.16. Measles 4.67. Tuberculosis 2.48. Whooping cough 1.99. Road traffic accidents 1.810. Protein-energy malnutrition 1.6
Total 61.2 (ID=56.5%)Mathers et al. in Global Burden of Disease and Risk Factors,
2006
Malaria
Manifestations
Burden
Interventions
Manifestations of the Malaria Burden
Infected Mosquito
Infected Human
Chronic effects
Anemia
Neurologic
Cognitive
Developmental
Impaired growth and development
Malnutrition
Acute febrile illness
Severe illness
Anemia
Hypoglycemia
Cerebral malaria
DeathRespiratory distress
Pregnancy
Fetus
MaternalAcute illness
Anemia
Low birth weight
Abortion, stillbirth
Infant and fetal mortality
Long-termsequelae
Long-termsequelae
Hypovolemia
Number of malaria deathsCause of malaria-related death
Cerebral malaria 110,000
Severe anemia 190,000-974,000
Respiratory distress 110,000
Hypoglycemia 153,000-267,000
Low birth weight 62,000-363,000
Total deaths from malaria 625,000-1,824,000
Deaths from Malaria: Children Under Fiveand Total, Africa 2001
962,000-2,806,000
● Under fives
● 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).
Source: Lopez, Begg, and Bos 2006.
Under-Five Deaths from AIDS, Malaria, and Other Causes, per Thousand Births, 1990 and 2001, Sub-Saharan Africa
Source: World Bank 2004 (CD-ROM version).
Rate of Progress in Reducing Under-Five Mortality, 1960-2000: China, India, Latin America, andSub-Saharan Africa
Plasmodium falciparum in 2002Clinical Cases
Region Population at risk (million)
Cases (M) (%)(million)
Africa 521 365 (215 - 374) (57%)
Americas 55 4 (2 - 8) (1%)
South East Asia
1,314 119 (66 - 224) (34%)
Western Pacific 142 15 (9 - 26) (4%)
Eastern Med. 176 12 (5 - 25) (4%)
Europe 4 1 (0 - 1) (<1%)
Total 2,211 515 (298 – 659) (100%)Snow et al, Nature 2005
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
Mil
lio
ns
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
846
423
188
1919
960
400
Feb
rile Illness
Malaria
J. Breman, AJTMH, 20011995 2020
Environmental and Behavioral
Modification
Genetic modification
of vectorsFuture Interventions
Vaccines (preerythrocytic,
blood stage, transmission-
blocking)
Protection (insecticide-impregnated
materials)
Control of the Malaria Burden
Current Interventions
Drugs (treatment, prevention)
Insecticides (house
spraying, larvicides)
0 5 10 15 20 25 30
Intermittent preventive treatment in
pregnancy with drug switch
Insecticide-treated bed nets
Insecticide residual spraying
Intermittent preventive treatment/
pregnancy (SP)
Cost-effectiveness ratio ($ per DALY averted)
Cost-Effectiveness of Interventions Against Malaria in
Sub-Saharan Africa
R. Laxminarayan et al (DCPP authors), 2006 in Disease Control Priorities in Developing Countries
Table 21.6. CERs for ITNs, IRS, and IPT
InterventionMean cost perDALY averted 90 percent range
ITNs (net + insecticide treatment)
Deltamethrin 11 5-21
Permethrin (1 treatment) 12 6-20
Permethrin (2 treatments)
17 9-31
ITNS (without provision of nets)
Deltamethrin 5 2-7
Permethrin (1 treatment) 6 3-9
Permethrin (2 treatments)
11 6-17
IRS (1 round)
DDT 9 5-13
Deltamethrin 10 6-14
Lambda-cyhalothrin 10 6-14
Malathion 12 8-18
Table 21.6. CERs for ITNs, IRS, and IPT (2)
InterventionMean cost perDALY averted 90 percent range
IRS (2 rounds)
DDT 17 11-24
Deltamethrin 18 12-27
Lambda-cyhalothrin 19 12-28
Malathion 24 15-34
IPT
Incremental costs 13 9-21
Average costs 24 16-35
Incremental Cost-Effectiveness Ratio of an
Intervention Costs B – Costs A
Effectiveness B –
Effectiveness A
Interventions studied:
personal = 204 population = 115
0 200 400 600 800 1,000 1,200 1,400 1,600
HIV/AIDS - peer programs
Voluntary counseling/testing
STI diagnosis/treatment
Condom promotion/distribution
Blood/needle safety
Tuberculosis coinfection
prevention/treatment
Mother/child prevention
Home care
Antiretroviral treatment
Cost-effectiveness ratio ($ per DALY averted)
Cost-Effectiveness of Interventions Against HIV/AIDS in Sub-Saharan Africa
Laxminarayan et al (DCPP authors), 2006, in Jamison et al, Disease Control Priorities in Developing Countries
Most current interventions are cost-effectivei.e. moderately effective, very cheap
1
10
100
1000
10000
100000
Co
st/
DA
LY
ga
ine
d (
US
$)
$1 per day gained
Endemic TB (DCP Project 2006)
Tuberculosis
TB control programmes were not able to spend all of their funds in 2004
0
20
40
60
80
100
China
Niger
ia
Ethio
pia
Brazil
Indone
sia
India
DR Cong
o
Philipp
ines
Viet N
am
Cambodi
a
Mya
nmar
Russia
Bangl
ades
h
Pakis
tan
Kenya
Moz
ambi
que
UR Tan
zani
a
Exp
end
itu
re/a
vaila
ble
fu
nd
ing
(%
)
The Neglected Tropical Diseases: Humanity’s Ancient Diseases of Stigma and Poverty
13 Parasitic and Bacterial Infections Rural Areas of Low-Income Countries Poverty-Promoting Conditions
Child Development & Education Pregnancy Worker Productivity
Burdened humanity for centuries “The Biblical Diseases”
Disabling and deforming Associated with intense stigma
River Blindness Guinea Worm Lymphatic Filariasis
Leprosy
Ranking of Communicable Diseases By DALYs
Disease Condition Disease Burden
HIV-AIDS 84.5 million
Neglected Tropical Diseases 56.6 million
Malaria 46.5 million
Tuberculosis 34.7 millionHotez PJ, Molyneux DH, Fenwick A, Ottesen E, Ehrlich Sachs S, Sachs JDPLoS Medicine 2006; 3: e102
1 10 100 1,000 10,000
Soil-transmitted helminths:
Albendazole
Leishmaniasis: casefinding and treatment
Onchocerciasis: Ivermectin
Trachoma: trichiasis surgery
Trachoma: drugtreatments
Cost-effectiveness ratio ($ per DALY averted)Source: DCPP Authors
Cost-Effectiveness of Interventions Related to Low-Burden Diseases in LMICs; Helminths,
Leishmaniasis, Onchocerciasis, Trachoma
“Best Buys”Neglected Opportunities
“Best Buys”
Neglected Opportunities in Sub-Saharan Africa (SSA)
and South Asia (SA) (1)
Low Cost Opportunity
Cost per DALY
averted ($)
Burden of disease
DALYs (106)
● Childhood Immunization
- Second measles
vaccination
- Increase coverage
- DTP, polio, measles, BCG
SSA
SA
1 – 5
8
13.5 – 31.3
28.4
● Traffic Injuries
- Increase speeding
penalties
- Speed bumps
SSA
SA
2 – 12
not evaluated
6.4
not evaluated
Laxminarayan et al (DCPP authors), 2006, in Jamison et al, Disease Control Priorities in Developing Countries
Higher Cost Buys
Perspective: Cost-Effectiveness and Coverage
Interventions to scale back
Interventions for which scaling up
is inefficient
Cost-effectiveinterventions used widely
Neglected opportunities
Current Coverage
Co
st E
ffect
iven
ess
Low High
Low
Hig
h
Laxminarayan et al, 2006, in Jamison et al, Disease Control Priorities in Developing Countries, 2nd ed.
Perspective: Cost-Effectiveness and Coverage
HIV/AIDS poor treatment
adherence(programs)
deep brain stimulation
Malariadrugs,
insecticide treated nets
Leishmaniasis treatment
Avertable Burden of Disease
Co
st E
ffect
iven
ess
Low
Hig
hLo
w
High
Laxminarayan et al, 2006, in Jamison et al, Disease Control Priorities in Developing Countries, 2nd ed.
Parkinson’sdisease
A Million Dollars Invested
How Much Health Will a Million Dollars Buy?
Service or InterventionReducing under-5
mortality Expanding
immunization coverage (EPI diseases)
Switch to artemisinin-combination therapy (ACT) where malaria is drug-resistant
Improved neonatal care (newborn resuscitation)
Adding vaccines to EPI (Hib and hepatitis B)
DALYs Averted ($ per DALY)
50,000-500,000 ($2-20)
50,000-125,000 ($8-20)
2,500-100,000 ($10-400)
4,000-24,000 ($40-250)
Research and Product Development
Share of Disease Burden Averted with Existing, Improved or New Interventions
Not avertable, research needed
Avertable with current interventions and coverage
0
a
b
c
Effective coverage
Source: WHO, 1996. Investing in Health Research and Development
Avertable if cost-effective interventions applied more widely
Avertable only with interventions that are less cost-effective
Research Needs
Efficacy of
Control Methods
High HighTraining
Some HighModerateResearch Support Needs
Low Low
Research, Training, and Support Needs According to Understanding of Diseases and
Efficacy of Control Methods
Research Needs
Efficacy of
Control Methods
High HighTraining
Some HighModerateResearch Support Needs
Low Low
SmallpoxGuinea wormPoliomyelitisH. influenzae type BMeaslesTetanus
MalariaDengue
HIV/AIDSInfluenzaTuberculosis
CancersAlzheimers
Research, Training, and Support Needs According to Understanding of Diseases
and Efficacy of Control Methods
Onchocerciasis Diarrheal diseases
Expected Results of R&D
New basic knowledge• Mechanisms of disease• Epidemiology and risk factors• Disease modeling and surveillance
New and improved tools• Drugs• Vaccines• Diagnostics• Devices• Prostheses and equipment• Vector control• Environmental modification• Behavioral, social, and economic change
Expected Results of R&D (2)
New and improved intervention methods
• Treatment algorithms and guidelines
• Intervention packaging
• Costing and cost-effectiveness
• Delivery: health systems and health services
Condition
GlobalDiseaseBurden (million)DALYs*
R&DFunding
($Millions)
R&DFunding
per DALY*
Cardiovascular 148.190 9402 $63.45
HIV/AIDS 84.458 2049 $24.26
Malaria 46.486 288 $6.20
Tuberculosis 34.736 378 $10.88
Diabetes 16.194 1653 $102.07
Dengue 0.616 58 $94.16
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
Main Messages
[Better data are needed]
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)
The Age Distribution of Deaths Under Age-5, Low- and Middle-Income Countries, 2001
Total deaths, including stillbirths = 13.758 million
23%
28%
25%24%
0%
5%
10%
15%
20%
25%
30%
Stillbirths Neonatal deaths Post-neonatal infant deaths(aged 28 days to 1 year)
Child deaths (aged 1 toless than 5 years)
Age category
Per
cen
t d
istr
ibu
tio
n o
f d
eath
s u
nd
er A
ge-
5
D. T. Jamison, et al, 2006 in Global Burden of Disease and Risk Factors
Main Messages2. 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.
Source: Dr. Anthony Fauci, 2005
Main Messages
3. “Very good buys”, infectious disease control/prevention
Vaccination Malaria control HIV prevention
4. “Not so good buys”
Treatment of latent TB, no HIV Treatment of HIV/AIDS if poor adherence
Main Messages5. Continued generation and diffusion of new knowledge and products are key to
improvements in health in the 21st century. Future investment is needed:
• Research and development
• Training leaders in research and operations; strengthening institutions
• Focus on low- and middle-income countries
• Collaboration and shared goals
Vertical Disease Control
Horizontal Disease Control
Integrated Disease Control
Books Published by Oxford University Press for DCPP in 2006
Disease Control Priorities in Developing Countries, second edition
Priorities In Health
Global Burden of Disease and Risk Factors
Rank South Asia(GNI: $450)
Sub SaharaAfrica
(GNI: $460)
East Asia and thePacific
(GNI: $900)
Europe andCentral Asia(GNI: $1,970)
Middle East andNorth Africa(GNI: $2,200)
Latin Americaand the
Caribbean(GNI: $3,580)
High–incomecountries
(GNI: $26,500)
1 Perinatalconditionsa
HIV/AIDS Cerebrovasculardiseases
Ischemic heartdisease
Ischemic heartdisease
Perinatalconditionsa
Ischemic heartdisease
2 LowerRespiratoryinfections
Malaria Perinatal onditionsa
Cerebrovasculardiseases
Perinatalconditionsa
Unipolardepressivedisorders
Cerebrovasculardiseases
3 Ischemicheartdisease
LowerRespiratoryinfections
Chronic obstructivepulmonary disease
Unipolar depressivedisorders
Traffic accidents Homicide andviolence
Unipolardepressivedisorders
4 Diarrhealdiseases
Diarrhealdiseases
Ischemic heartdisease
Self-inflictedinjuries
Lower respiratoryinfections
Ischemic heartdisease
Alzheimer andother dementias
5 Unipolardepressivedisorders
Perinatalconditionsa
Unipolar depressivedisorders
Chronic obstructivepulmonary disease
Diarrheal diseases Cerebrovasculardiseases
Tracheal andlung cancer
Note - GNI: GNI per Capita (US$); a) This cause category includes ‘conditions arising in the perinatal period’(less or equal to 28 days) as defined in the International Classification of Diseases, principally low birthweight, prematurity, birth asphyxia, and birth trauma, and does not include all causes of deaths occurring in the perinatal period.
Source: Mathers, CD., Lopez A.D., and Murray CJL, 2006; World Development Indicators, 2003
Table 2.