Why is child mortality so different
across countries and regions with
similar income levels ?
Peter Boone
May 2005
Questions:
• Why is child mortality so different across
countries and regions with similar income
levels ?
• Is it possible to replicate the low levels
observed in some countries quickly in a
RCT ? (at low cost ?)
Child mortality and income
Child Mortality Rate
GNB
MWI
200
150
MRT
GIN
CMR
SWZ
100
NPL
UZB
50
MDA
ZAF
VNM
LKA
CUB
0
6
6.5
7
7.5
8
8.5
Ln PPP GDP per capita
9
9.5
10
Case Study: Kerala
• State created in 1956
• Communist government elected 1957
• 1993 and 1998/9 FHS provide large
database
• Literature reports improvements in almost
every area of health as reason for Kerala’s
relative success
Child mortality in Indian States
160
Child Mortality Rate
140
Mad
Utt Meg
Raj
Bih
Ori
Aru
India
Ass
Guj
Jam And
Har Pun
Tri
ar Tam
KNag
Ben
Mah
Man
Miz
Him
120
100
80
60
40
20
Del
Goa
Ker
0
0.0
5.0
10.0
15.0
Per Capita Net State Domestic Product
('000 Rupees 1996)
20.0
25.0
Focus on ARI and Diarrhoea
Cause of non-neonatal child death by major disease/syndrome
33%
13%
32%
Source: Black et. Al. 2005
Diarrhea
Pneumonia
Malaria
Other
AIDS
Measles
Unknown
Pathogens causing diarrhoea
Presentation
Organism
Acute watery
diarrhoea
Salmonella, Staphylococci, B. cereus, C.
perfringens, V. parahaemolyticus, Ecoli, Rotavirus
+ other enterovirsues, Cryptosporidium, V. cholerae
Acute bloody
diarrhoea
Shigella sp., C. jejuni
Chronic
diarrhoea
G. intestinalis
Chronic
diarrhoea with
blood
E. Histolytica, B. coli, S. mansoni
Source: Webber (2005)
Pathogens causing ALRI
Presentation
Organism
Pneumonia
Streptococcus pneumoniae,
Haemophilius influenzae, Influenza A
or B, RSV, Adenoviruses,
Morbillivirus, Metapneumorvirus, and
many more…..
Meningitis
Neisseria meningitis, Haemophilius
influenzae, Streptococcus
pneumoniae, Mycobacterium
tuberculosis, Staphlycocci,
Escherichia coli, Group B
streptococci, Mumps virus, Rubella
virus, and many more….
Source: Webber (2005)
Steps to child mortality and
possible interventions
Exposure
Improve
sanitation,
water,
hygiene
Clinical
Manifestation
Raise
immune
response:
Better
nutrition and
vaccines
Treatment
Improve health seeking
decisions: education,
proximity of services,
cost of services
Outcome
Raise healthcare
worker training and
incentives, medical
supplies, new
treatments
Which stage is best targeted ?
• No consistent answer in the literature
– Low CMR countries intervened in all areas
• Cuba, Sri Lanka, Kerala, Former communist block, Costa
Rica
– Consensus that vaccines (Measles, DPT, BCG) have
been highly successful but Diarrhoea and ALRI not
easy targets
– Controlled trials demonstrate potential large impact of
interventions at every stage
– Cost effectiveness work (e.g. World Bank 1993) helps
allocate resources across interventions but can’t
capture synergies, social and institutional issues that
could lead to a different package.
Two alternative hypotheses
For groups with similar income levels:
A. Healthier populations have reduced
exposure to disease, and hence less
morbidity and less mortality.
B. Healthier populations have similar morbidity
but lower case fatality rates.
Exposures & Morbidity
• DHS surveys compare disease incidence
across low income countries.
• Sanitation, water and hygiene are the
main interventions aimed to reduce
pathogen exposures. International data is
available.
ARI and Diarrhoea Incidence
(31 low income countries)
ARI: average cases per year per child
10
NER
9
8
SDN
7
MDG
6
TCD
ETH
LBR
5
GAB
4
KAZ
TZA
3
PHL
2
MDG
KHM
MWI
VNM
BWA
BGD
1
0
0
2
4
6
Diarrhoea: average cases per year per child
8
10
Mortality and Disease Incidence
Ln (Child Mortality Rate)
Coef
SE
Ln (PPP GDP per capita)
-3.073**
1.906
Ln (PPP GDP per capita)2
0.184**
0.127
Diarrhoea (under age 5 cases per yr)
0.057
0.050
ARI (under age 5 cases per yr)
0.017
0.041
Measles vaccine (proportion popn)
-1.005++
0.488
Doctors per 100,000
-0.279++
0.133
R2
0.732
N
31
** : Jointly significant at 5% level
++: Significant at 5% level
Mortality and Sanitation/Water
Ln (Child Mortality Rate)
Coef
SE
Ln (PPP GDP per capita)
1.057**
0.546
Ln (PPP GDP per capita)2
-0.103**
0.032
Improved Sanitation (proportion popn)
-0.163
0.218
Improved Water (proportion popn)
-0.160
0.311
Measles vaccine (proportion popn)
-0.103**
0.646
DPT Vaccine (proportion popn)
-1.051**
0.577
Doctors per 100,000
-0.202++
0.044
R2
0.869
N
103
**: Jointly significant at 1% level (vaccines; income measures grouped separately)
++: Significant at 1% level
Mortality and Latrine Access
-1
-.5
0
.5
1
(103 countries)
0
20
40
60
80
% of population with access to latrines
100
India: ARI and Diarrhoea Incidence
(26 States, children aged <4)
25
ARI Incidence (%)
Tri
20
15
Man
Ass
Ben
10
5
Ker Nag
India
Raj
Goa Kar Pun
0
0
5
Tam
Ori
Aru
Him
Bih
20
15
10
Diarrhoea Incidence
(% in previous two weeks, < 4 yr olds)
Jam
Miz
25
India: Mortality and Disease Incidence
(26 states)
Ln (Child Mortality Rate)
Coef
SE
Ln (SDP per capita)
-0.0379
0.2011
Diarrhoea (under age 5 cases per yr)
0.0357
0.0344
ARI (under age 5 cases per yr)
-0.0482
0.0482
All rec’d vaccines (proportion popn
aged<4)
-1.4000++
0.3412
R2
0.54
N
26
** : Jointly significant at 5% level
++: Significant at 5% level
ris
M
ad
ya
sa
Bi
h
Pr ar
U
a
H ttar des
im
h
ac P ra
ha de
An l P sh
dh ra
ra de
Pr sh
ad
R esh
aj
a
T a st h a
m
n
il
N
ad
u
In
Ka
d
rn ia
at
a
H ka
W ar y
es an
tB a
en
g
G al
u
M
ah jara
Ja ara t
m
s
m htr
u
a
R
eg
io
Pu n
n
M
eg jab
ha
la
ya
G
oa
As
Ar
sa
un
m
Tr
ac
ha ipu
lP
r
ra a
de
s
N
ag h
al
an
d
Ke
ra
M la
an
ip
ur
D
e
M lhi
iz
or
am
O
100
% of households with access to latrines
India: Household access to latrines
120
80
60
40
20
0
M
M
oa
ad
iz
ya ora
m
Pr
ad
es
h
O
r
R issa
a
Ja
ja
s
m
m th a
u
n
R
eg
H
io
im
n
ac
ha Bih
l P ar
ra
de
sh
An
dh
In
Ar
r
un a P dia
ra
ac
ha de
l P sh
r
M ad
ah es
h
ar
as
ht
r
G a
uj
ar
a
Tr t
i
T a pu
ra
m
il
U
N
tta
r P adu
ra
d
Ka es
rn h
at
a
H ka
a
r
W
es yan
tB a
en
ga
l
D
el
h
Pu i
nj
ab
G
a
N
ag la
M alan
eg
d
ha
la
ya
M
an
ip
u
As r
sa
m
Ke
r
% of households with piped or pumped water
India: Access to improved water
supply
120
100
80
60
40
20
0
Latrines and Diarrhoea Incidence
Diarrhea incidence
(children <4 yrs %)
35
Jam
Him
30
Ori
25
20
Bih
15
Tri
Mah
Mad
Utt
Meg
Raj India Guj
Goa
And
Aru
Nag
Ben
Pun
Miz
Man
Tam
Har
Kar
10
Del
Ker
Ass
5
0
0
20
40
60
Households with latrines
(%)
80
100
Diarrhea and Water/Sanitation:
Trial results
Interventions vs Diarrhoea
50
45
40
35
30
% risk reduction
25
20
15
10
5
0
water
quality
Source: Val Curtis
water
quantity
sanitation
hygiene
prom
hand
wash
Implication: Disease incidence and
mortality
• Disease incidence is weakly correlated
with mortality
• Sanitation and water improvements are
weakly correlated with mortality
• No evidence from survey data that
Kerala’s success is due to lower morbidity
B. Treatment regimes
• Treatments in theory should be able to stop
most mortality
– Treatment trials wr to ARI and Diarrhea at healthcare
centers typically have miniscule case fatality rates
– Population-based RCT with frequent participant
monitoring have low mortality rates
• Regressions across countries and within India
suggest treatment variables (vaccines,
physicians) are more important than incidence
measures
Treatment Protocol (WHO)
Presentation
Treatment
Suspected ALRI: Cough
and rapid breathing
Antibiotics at home, at 0.0%
hospital if severe
$0.50-$2.00 per course
at home
Diarrhea
-Watery
- ORT
-Bloody
- Antibiotics
Suspected Malaria
- Fever, parasites in blood
(if measured)
- Antimalarial
chemoprophylaxis
Source: Work in progress
Case fatality if
treated early and
cost
0.0%, 10 cents per
packet
0.0%, $0.50-$2.00 per
course at home
Near 0%, $0.25-$5.00
per course
Surprising longevity of control study
participants (if you visit them)….
Study
Location
Luby et. al,
2005
Pakistan
Participants Baseline
(intervention, mortality
control)
3,163 ; 1,528 CMR 140
90 nonneonatal
Schellenber Tanzania 350 ; 351
IMR 100
g et. al. 2003
60 nonneonatal
The studies were not powered to measure mortality change
Study
mortality rate
(intervention;
control)
24 ; 38
20 ; 23
Treatment proxies and mortality
(31 countries)
Ln (Child Mortality Rate)
Coef
SE
Ln (PPP GDP per capita)
-3.073**
1.906
Ln (PPP GDP per capita)2
0.184**
0.127
Diarrhoea (under age 5 cases per yr)
0.057
0.050
ARI (under age 5 cases per yr)
0.017
0.041
Measles vaccine (proportion popn)
-1.005++
0.488
Doctors per 100,000
-0.279++
0.133
R2
0.732
N
31
** : Jointly significant at 5% level
++: Significant at 5% level
India: Treatment proxies and Mortality
(26 states)
Ln (Child Mortality Rate)
Coef
SE
Ln (SDP per capita)
-0.0379
0.2011
Diarrhoea (under age 5 cases per yr)
0.0357
0.0344
ARI (under age 5 cases per yr)
-0.0482
0.0482
All rec’d vaccines (proportion popn
aged<=3)
-1.4000++
0.3412
R2
0.54
N
26
** : Jointly significant at 5% level
++: Significant at 5% level
India: Vaccine coverage
All Recommended Vacines
(children <4 yrs)
100
90
80
70
60
50
40
30
20
10
0
Goa
Guj
Ben
Utt
Mad
Aru
Raj
Nag
Bih Meg
Tri
India
Man
Ker
Pun
Har
Kar
And
Tam
Ass
0
20
40
60
Measles Vaccine
(%)
80
100
India: Proximity to health care and
spending on healthcare
Population with healthcare
facilities in village (%)
120
100
Ori
Ker
80
60
Bih
40
20
0
0.00
Goa
Tam
Pun
Him
Raj
20.00
Aru
40.00
60.00
State healthcare expenditures per capita (Rp)
80.00
Why differences in treatment ?
• Poverty/Price ?
– How do household’s value treatment without
knowing its potential benefit ?
• Coordination and regulation failure ?
– In Kerala, 2/3 of treatments are done by the
private sector
• Knowledge (both within the health system
and within the family) ?
– Essential to make health decisions….
Two sorts of “health knowledge”
• Selected behavior in species
• Acquired knowledge
Disgust: Selected mechanism to
control disease
• With child mortality rates at 40% over a
long history, small deviations in behavior
due to genetic factors that raised odds of
survival would eventually dominate the
population
• Our sense of disgust and beauty is
probably intrinsically related to the fight
against microscopic enemines
Two fluids
x= 1.6
x= 2.6
x= 1.6
x= 3.9
Source: Val Curtis
3.6 vs. 4.6
Households that heard of AIDS
(%)
Knowledge of AIDS and ORT
100
Man
Tam
80
Del
Nag
Ker Miz
Goa
Mah
Aru
Kar
Pun
And
Tri
Meg
India Har
Ori
Ass
Jam
Guj
Ben
Mad
Raj
Utt
60
40
20
Bih
0
30
50
70
Households that know of ORT
(%)
90
Him
or
am
K
er
al
O a
ris
M sa
an
ip
ur
D
el
T r hi
H
im N ipu
ac ag ra
ha a l
l P an
ra d
de
s
P h
un
H j ab
ar
ya
n
A a
A
s
ru K sa
na ar m
ch na
t
M al P aka
ad r
ya ad
Ja P esh
m rad
m
u esh
R
M eg
eg i o
ha n
la
ya
B
ih
ar
U
tta In
rP d
ra ia
de
A
sh
nd
hr
a Go
P
ra a
de
G sh
T a uj a
m ra
M il N t
ah a
ar du
a
R sht
a r
W j as a
es th
t B an
en
ga
l
M
iz
% of households with access to latrines
Should you reduce fluids when a
child has diarrhoea ?
70
60
50
40
30
20
10
0
Uganda: Perceived causes of Malaria
What causes Malaria ?
Mosquitoes
%
Comment:
95.3 Most believed transmitted by
drinking eggs or larvae
Bad air
30.8
Contagious from others
51.5
Drinking water
67.0
Witchcraft
Convulsions cannot be
cured by modern
medicine:
Source: Nuwaha (2002)
9.8
51.0
What causes a common cold ?
(Massachusetts, 197 families)
Virus
Germs
93%
88%
Bacteria
Changes in the weather
Not enough clothes
66%
60%
56%
Wet hair in cold weather
41%
Cold weather
Teething
38%
28%
Walking barefoot
26%
Source: Lee et. al. (2005)
Tanzanian RCT healthcare quality
Assessment Indicators
IMCI Non-IMCI
(%)
(%)
P-Value
Pneumonia correctly treated
75
40
<0.01
Malaria correctly treated
88
25
<0.001
Child needing antibiotic
/antimalarial prescribed correctly
73
35
<0.001
Child not needing an antibiotic
leaves with an antibiotic
14
43
<0.001
Child needing vaccinations gets all
needed
12
0
>0.10
Caretaker of sick child advised to
give extra liquids and continue
feeding
90
4
<0.00`
Conclusion
Exposure
Clinical
Manifestation
Treatment
Outcome
Treatment variations probably explain the differences in mortality at
similar income levels across regions and countries. An underlying
factor leading to differerences in treatment outcomes may be
variations in the perceived (and actual) value of existing available
treatments.
Next steps
• Conduct one or more RCT with the goal being to reduce
mortality sharply in a high mortality region through
changes in the treatment regime
– Preliminary research to understand treatment seeking, quality of
healthcare in selected region
– Outreach program in RCT - Intervention arm:
• provide information to mothers on disease recognition and
treatment
• monitor child’s health frequently to ensure treatment regime has
changed
• free provision of treatment and vaccination coverage
• Antenatal and neonatal program
– Follow-up studies to measure duration of impact and changes in
treatment seeking behavior once free assistance is ended
SOAP Trial Africa
• Objectives:
– Determine the impact of an outreach program,
including treatment for children that develop
disease, on child mortality
– Determine the impact of hand-washing
behavior on incidence of acute lower
respiratory infections and diarrhoea, and on
the need for treatment
SOAP Trial Africa
Neighborhoods: High mortality region
(randomized to intervention arms or control)
Households within intervention
neighborhoods randomized
to intervention arms
Arm 1:
Handwashing & treatment
800 children
Note: Suggested structure
Arm 3:
Mortality tracked
2800 children
Arm 2:
Treatment
800 children
SOAP Trial: Endpoints
• Comparison of incidence of ALRI and Diarrhoea
in Arm 1 vs Arm 2
– Powered at 80% to capture a 25% reduction in ALRI
in Arm 1
• Comparison of mortality in Arm 1 + Arm 2 versus
Arm 3
– Powered at 80% to capture a 60% reduction in child
mortality (assuming control 100 CMR)
• Comparison of the cost of treatment in Arm 1
versus Arm 2
SOAP Trial: Other components
• Surveys to understand (before and/or after
the study):
– Baseline disease incidence, mortality, and
household characteristics
– Hygiene behavior and beliefs
– Treatment seeking behavior and beliefs
– Quality of care in existing healthcare centers
SOAP Trial: Timeline
• Agreement on study design and structure
– Within one month
• Location, local partner, detailed protocol
– End 2005
• Randomization
– 1Q 2006
Cause of neonatal deaths
16%
24%
7%
24%
Source: Black et. al., 2005
29%
Severe Infections
Birth Asphyxia
Prematurity
Tetanus
Other
Naandi Neonatal deaths trial
• Objectives
– To determine the impact on neonatal mortality
of a targeted outreach and education program
Neonatal Mortality Trial
Villages:
(randomized to intervention arms or control)
Intervention Arm:
Monthly education and healthcare visits
Screening for high risk families
Targeted outreach program
(2000 births)
Note: Suggested structure
Control Arm
Delayed introduction
(2000 births)
Naandi Trial: Timeline
• Decision whether in principle we wish to
proceed (within 3 months)
• Study team selected to work out detailed
timeline and program (6 months)
• Start surveys and trial in 2006