Transcript Combating Infectious Diseases and the Disease Control Priorities Project: A Convergence of Epidemiology, Economics and Research Joel G.

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

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)
LMICs (% total deaths)
(n =7.89 million (14%)
(n = 48.35 million (86%)
1.
2.
3.
4.
5.
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)
1.
2.
3.
4.
5.
Ischemic heart disease (11.8)
Cerebrovascular disease (9.5)
Lower respiratory
infections (7.0)
HIV/AIDS (5.3)
Perinatal conditions (5.1)
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
High Income (% total deaths)
LMICs (% total deaths)
(n = 7.89 million (14%)
(n = 48.35 million (86%)
6.
7.
8.
9.
10.
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%)
6.
7.
8.
9.
10.
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%)
Mathers et al., 2006, in Lopez et al, Global Burden of Disease and Risk Factors
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
Disability-Adjusted Life Years (DALYs)
Countries
Low- and
Middle-Income
High Income
Total
For infectious
For all
Infectious
and parasitic
diseases
Population in diseases, no. diseases, no.
millions (%) in millions (%) in millions (%) burden (%)*
5,219
(85)
1,387
(90)
321
(99)
29
929
(15)
149
(10)
3
(1)
4
(100)
27
6,148 (100)
1,536
(100)
*includes respiratory infections
Mathers et al, 2006, in Lopez et al, Global Burden of Disease and Risk Factors
324
Leading Causes of Disability-Adjusted
Life Years (DALYs), Globally, 2001
(n = 1.54 billion)
Cause
% total
Perinatal conditions
5.9
2.
Lower respiratory infection
5.6
3.
Ischemic heart disease
5.5
4.
Cerebrovascular disease
4.7
5.
HIV/AIDS
4.7
6.
Diarrheal diseases
3.9
7.
Unipolar depressive disorders
3.4
8.
Malaria
2.6
9.
Chronic obstructive pulmonary disease
2.5
10. Tuberculosis
2.3
Total
(ID= 19.1%) 41.1
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)
Infectious
For infectious
diseases
For all diseases, and parasitic
burden in
Population in no. in millions diseases, no.
in millions (%) region,%*
Region
millions (%)
(%)
Sub-Saharan Africa
668 (13) 345
(25)
173
(54)
59
South Asia
1,388
(27)
409
(29)
88
(27)
310
(6)
66
(5)
7
(2)
16
1,850
(35)
346
(25)
37
(12)
14
Latin America/Caribbean 526
(10)
104
(8)
10
(3)
13
(9)
117
(8)
5
(2)
6
320
(100)
29
Middle East/North Africa
East Asia/Pacific
Europe/Central Asia
Total
477
5,219 (100) 1,387
(100)
*includes respiratory infections
Mathers et al, 2006, in Lopez et al, Global Burden of Disease and Risk Factors
31
Infectious Burden, Low- and Middle-Income Countries,
by World Bank Region, 2001
Disease
Disease Burden
In LMICs
DALYs, % SSA
Disease burden by region, %
SA
ME/NA
EA/P
LA/C
E/CA
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
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
0.7
23.5
40
39
4
9
5
2
STD
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
Leading Causes of Disability-Adjusted Life Years
(DALYs) in Sub-Saharan African Region, 2001
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Total DALYs
HIV/AIDS
Malaria
Lower respiratory infections
Perinatal conditions
Diarrheal diseases
Measles
Tuberculosis
Whooping cough
Road traffic accidents
Protein-energy malnutrition
Total
%
17.8
10.3
8.4
6.3
6.1
4.6
2.4
1.9
1.8
1.6
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
Anemia
Acute
febrile
illness
Severe illness
Infected
Mosquito
Hypoglycemia
Long-term
sequelae
Respiratory
distress
Hypovolemia
Death
Cerebral malaria
Anemia
Infected
Human
Chronic
effects
Neurologic
Cognitive
Impaired
growth and
development
Malnutrition
Developmental
Fetus
Low birth weight
Abortion, stillbirth
Pregnancy
Maternal
Acute illness
Anemia
Infant and fetal
mortality
Long-term
sequelae
Deaths from Malaria: Children Under Five
and Total, Africa 2001
Cause of malaria-related death
●
Number of malaria deaths
Under fives
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
Total, all ages*
962,000-2,806,000
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).
Under-Five Deaths from AIDS, Malaria, and Other Causes,
per Thousand Births, 1990 and 2001, Sub-Saharan Africa
Source: Lopez, Begg, and Bos 2006.
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).
Plasmodium falciparum in 2002
Clinical Cases
Region
Africa
Americas
South East Asia
Population at risk
(million)
Cases (M) (%)
(million)
521
365 (215 - 374) (57%)
55
4 (2 - 8) (1%)
1,314
119 (66 - 224) (34%)
Western Pacific
142
15 (9 - 26) (4%)
Eastern Med.
176
12 (5 - 25) (4%)
4
1 (0 - 1) (<1%)
Europe
Total
Snow et al, Nature 2005
2,211
515 (298 – 659) (100%)
Acute Febrile Episodes and Malaria-Associated Febrile Episodes
in African Children 0-4 years Living in Endemic Areas, 1995-2020
2000
1919
1800
1600
960
1000
Malaria
Millions
1200
846
800
600
400
423
400
188
200
0
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
1995
J. Breman, AJTMH, 2001
2020
Febrile Illness
1400
Control of the Malaria Burden
Current Interventions
Drugs
(treatment,
prevention)
Protection
(insecticideimpregnated
materials)
Insecticides
(house
spraying,
larvicides)
Environmental and
Behavioral
Modification
Vaccines
(preerythrocytic,
blood stage,
transmissionblocking)
Future Interventions
Genetic
modification
of vectors
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
Cost-effectiveness ratio ($ per DALY averted)
R. Laxminarayan et al (DCPP authors), 2006 in Disease Control Priorities in Developing Countries
30
Table 21.6. CERs for ITNs, IRS, and IPT
Mean cost per
DALY averted
90 percent range
Deltamethrin
11
5-21
Permethrin (1 treatment)
12
6-20
Permethrin (2 treatments)
17
9-31
Deltamethrin
5
2-7
Permethrin (1 treatment)
6
3-9
Permethrin (2 treatments)
11
6-17
9
5-13
Deltamethrin
10
6-14
Lambda-cyhalothrin
10
6-14
Malathion
12
8-18
Intervention
ITNs (net + insecticide treatment)
ITNS (without provision of nets)
IRS (1 round)
DDT
Table 21.6. CERs for ITNs, IRS, and IPT (2)
Intervention
Mean cost per
DALY 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
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
Tuberculosis
Most current interventions are cost-effective
i.e. moderately effective, very cheap
10000
1000
$1 per day gained
100
10
(-X
Tr
ea
ra
y)
ta
ct
iv
e
(+
tr
Tr
an
ea
s)
ta
ct
iv
e
(-t
Tr
ra
ea
ns
tn
)
on
-in
fe
ct
io
Tr
us
ea
tM
DR
(s
tn
d)
Tr
ea
tM
DR
(in
d)
TL
TI
ra
y)
(+
X
va
cc
ew
N
TL
TI
C
in
e
G
1
B
Cost/DALY gained (US$)
100000
Endemic TB (DCP Project 2006)
C
hi
N na
ig
Et eria
hi
op
ia
B
In r a
do z
ne il
si
a
D Ind
R
i
Ph Co a
ili ng
pp o
Vi ine
et s
C N
am am
bo
M d
y a ia
nm
a
B Ru r
an s
gl sia
ad
Pa esh
ki
st
an
M
K
oz e
am n y
a
U
R biq
Ta u
nz e
an
ia
Expenditure/available funding (%)
TB control programmes were not able to
spend all of their funds in 2004
100
80
60
40
20
0
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




Burdened humanity for centuries


Child Development & Education
Pregnancy
Worker Productivity
“The Biblical Diseases”
Disabling and deforming

Associated with intense stigma
River Blindness
Guinea Worm
Leprosy
Lymphatic Filariasis
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 million
Hotez PJ, Molyneux DH, Fenwick A, Ottesen E, Ehrlich Sachs S, Sachs JD
PLoS Medicine 2006; 3: e102
Cost-Effectiveness of Interventions 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
Cost-effectiveness ratio ($ per DALY averted)
Source: DCPP Authors
1,000
10,000
“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 ($)
Burden of
disease
DALYs (106)
●
Childhood Immunization
- Second measles
vaccination
- Increase coverage
- DTP, polio, measles, BCG
SSA
SA
1–5
8
13.5 – 31.3
28.4
●
Traffic Injuries
- Increase speeding
penalties
- Speed bumps
SSA
SA
2 – 12
not evaluated
6.4
not evaluated
Laxminarayan et al (DCPP authors), 2006, in Jamison et al, Disease Control Priorities in Developing Countries
Higher Cost Buys
High
Low
Cost Effectiveness
Perspective:
Cost-Effectiveness and Coverage
Neglected
opportunities
Interventions for
which scaling up
is inefficient
Low
Cost-effective
interventions
used widely
Interventions to
scale back
Current Coverage
High
Laxminarayan et al, 2006, in Jamison et al, Disease Control Priorities in Developing Countries, 2nd ed.
Perspective: Cost-Effectiveness and
Coverage
High
Leishmaniasis
Low
Cost Effectiveness
Malaria
treatment
Parkinson’s
disease
deep brain
stimulation
Low
drugs,
insecticide
treated nets
HIV/AIDS
poor treatment
adherence
(programs)
High
Avertable Burden of Disease
Laxminarayan et al, 2006, in Jamison et al, Disease Control Priorities in Developing Countries, 2nd ed.
A Million Dollars Invested
How Much Health Will a Million Dollars Buy?
Service or Intervention
Reducing under-5
mortality
 Expanding immunization
coverage (EPI diseases)
 Switch to artemisinincombination therapy
(ACT) where malaria is
drug-resistant
 Improved neonatal care
(newborn resuscitation)
 Adding vaccines to EPI
(Hib and hepatitis B)
DALYs Averted ($ per DALY)
50,000-500,000 ($2-20)
50,000-125,000 ($8-20)
2,500-100,000 ($10-400)
4,000-24,000 ($40-250)
Research and Product
Development
Share of Disease Burden Averted with Existing, Improved or New
Interventions
Not avertable, research needed
Avertable with
current
interventions and
coverage
0
Effective coverage
Avertable if costeffective
interventions
applied more
widely
a
Avertable only
with interventions
that are less costeffective
b
Source: WHO, 1996. Investing in Health Research and Development
c
Research, Training, and Support Needs
According to Understanding of Diseases and
Efficacy of Control Methods
High
High
Training
Efficacy
of
Control
Methods
Low
Research
Needs
Some
Moderate
Research Support Needs
High
Low
Research, Training, and Support Needs
According to Understanding of Diseases and
Efficacy of Control Methods
High
High
Training
Efficacy
of
Control
Methods
Smallpox
Guinea worm
Poliomyelitis
Influenza
H. influenzae type B
Measles
Tetanus
Low
Malaria
Dengue Research
HIV/AIDS
Needs
Some
Onchocerciasis
Diarrheal diseases
Moderate
Research Support Needs
Tuberculosis
Cancers
Alzheimers
High
Low
Expected Results of R&D
New basic knowledge
• Mechanisms of disease
• Epidemiology and risk factors
• Disease modeling and surveillance
New and improved tools
•
•
•
•
•
•
•
•
Drugs
Vaccines
Diagnostics
Devices
Prostheses and equipment
Vector control
Environmental modification
Behavioral, social, and economic change
Expected Results of R&D (2)
New and improved intervention methods
• Treatment algorithms and guidelines
• Intervention packaging
• Costing and cost-effectiveness
• Delivery: health systems and health services
Disease Burden and Research and Development Funding
Global
Disease
Burden
(million)
DALYs*
R&D
Funding
($Millions)
R&D
Funding
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
Condition
Dengue
0.616
58
$102.07
$94.16
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
Percent distribution of deaths under Age-5
30%
25%
28%
25%
24%
23%
20%
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
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.
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 Messages
5. 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
Please Visit Our Web Site at:
www.dcp2.org
Table 2.
Rank
South Asia
(GNI: $450)
Sub Sahara
Africa
(GNI: $460)
East Asia and the
Pacific
(GNI: $900)
Europe and
Central Asia
(GNI: $1,970)
Middle East and
North Africa
(GNI: $2,200)
Latin America
and the
Caribbean
(GNI: $3,580)
High–income
countries
(GNI: $26,500)
1
Perinatal
conditionsa
HIV/AIDS
Cerebrovascular
diseases
Ischemic heart
disease
Ischemic heart
disease
Perinatal
conditionsa
Ischemic heart
disease
2
Lower
Respiratory
infections
Malaria
Perinatal
onditionsa
Cerebrovascular
diseases
Perinatal
conditionsa
Unipolar
depressive
disorders
Cerebrovascular
diseases
3
Ischemic
heart
disease
Lower
Respiratory
infections
Chronic obstructive
pulmonary disease
Unipolar depressive
disorders
Traffic accidents
Homicide and
violence
Unipolar
depressive
disorders
4
Diarrheal
diseases
Diarrheal
diseases
Ischemic heart
disease
Self-inflicted
injuries
Lower respiratory
infections
Ischemic heart
disease
Alzheimer and
other dementias
5
Unipolar
depressive
disorders
Perinatal
conditionsa
Unipolar depressive
disorders
Chronic obstructive
pulmonary disease
Diarrheal diseases
Cerebrovascular
diseases
Tracheal and
lung cancer
Note - GNI: GNI per Capita (US$); 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