Seasonal malaria chemoprevention
& micronutrient supplementation
in pre-schools in Mali
Malaria, nutrition,
and child development
Improving health worldwide www.lshtm.ac.uk
Measurement of
biomedical outcomes
Siân Clarke
London School of Hygiene & Tropical Medicine, UK
Disease burden
child sponsorship programme supporting rural communities in Sikasso region, southern Mali
Sikasso and Yorosso cercles• Intense seasonal transmission with malaria risk concentrated in 6-7 month period
• 51% OPD visits under-fives due to malaria• 88% anaemia in children 0-5 years • 45% stunted, 16% wasted
• 61% primary school enrolment in rural areas• 36% primary school completion in rural areas
WHO Policy Recommendation: March 2012
Seasonal Malaria Chemoprevention (SMC) for P falciparum malaria control in highly seasonal transmission areas
of the Sahel sub-region in Africa
• Intermittent treatment during malaria season to maintain therapeutic antimalarial drug concentrations in the blood throughout the period of greatest risk
• SP+AQ: given monthly (max of 4 months)
• Aim: To prevent malarial illness
• Target: Children <5 years of age
• Only recommended for Sahel sub-region, where typically 60% rainfall within 3 months
Expected benefits:
• Prevent 75% all malaria episodes
• Prevent 75% severe malaria episodes
• Probably reduce moderate-severe anaemia
• May decrease child mortality by 1 in 1000
SikassoMali
Seasonal malaria chemoprevention
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Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
0-4 years
5-9 years
10-14 years
Rainy season Schools reopen
3-4 Monthly treatments
1 2 3 4
Drug: SP+AQ
Aim: To prevent clinical attacks
Target: <5 years
• Seasonal malaria chemoprevention
• Nutrition education and distribution of micronutrient powders (MNPs) to households
• Target population: children aged 3-59 months
Two interventions
Jul - Dec Jan-Jun
Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun
Rainy season
Consent
Seasonal malariachemoprevention
MNP Distribution
Evaluation
All children resident in community eligible to receive interventions (community-wide distribution)
ECCD centre as a rallying point – sensitization, training, distribution
Community responsible for administering interventions
Managed through existing school and ECCD management structures
Community-led, ECCD-centred
Checking age eligibility SMC treatment Observation post-treatment
Outcome : Reduced malaria prevalence, incidence of clinical attacks & childhood deaths
Outcome : Reduced iron deficiency and anaemia
Outcome : Gains in physical growth and reduced stunting
Malaria infection& clinical attacks
Deworming and Vitamin A (by government)
Intestinal helminths and Vitamin A deficiency
Undernutrition and iron deficiency
Seasonal Malaria Chemoprevention
Iron and Micronutrient supplementation
Hypothesised causal chain
Improved school readiness and educational attainment
Improved physical, cognitive, linguistic and socio-emotional development
Parenting sessions
Low literacy environment
60 communities with ECCD centres
30 communities with no ECCD
Randomised
Study armIntervention
30 communitiesControl
30 communitiesComparison
30 communities
Interventions2013 – 2015
• ITNs• Deworming/Vit A• Malaria – SMC • Nutrition – MNPs• Parenting
• ITNs• Deworming/Vit A
• Malaria – SMC
• Parenting
• ITNs• Deworming/Vit A
• Malaria – SMC
EvaluationMay-Jun 2016
600 children - 3y600 children - 5y
600 children - 3y600 children - 5y
600 children - 3y600 children - 5y
Trial design
Does improved malaria control and nutrition interventions in early childhood:
Reduce prevalence of asymptomatic malaria infection?
Reduce prevalence of anaemia [primary outcome]?
Reduce prevalence of stunting?
Reduce prevalence of underweight?
Reduce prevalence of acute malnutrition?
Improve cognitive foundation skills for early literacy?
Improve school readiness?
Outcomes
Evaluation
Surveys in May-June 2014, 2016 3 years 5 years
Biomedical surveys – malaria, anaemia, growth
Cognitive surveys – foundation skills for learning
IDELA – Int. Development & Early Learning Assessment
0
Parental interviews
• effective coverage of interventions, acceptability, daily practicalities, barriers to use, adverse events
• home literacy environment, cognitive stimulation activities in the home
Qualitative evaluation – post-intervention
Nutrition & growth
Indicators
Height-for age HAZ Stunting Chronic undernutrition
Weight-for age WAZ Underweight Chronic undernutrition
Height-for-height WHZ Wasting Acute undernutrition
More than 2 SD below the mean (2006 WHO standard popn)
Standard population: Breastfed children of varying ethnicity raised under optimal conditions
Expect 2.5% of individuals in a normal population to fall below 2 SD
Nutrition & growth
Challenges :
Accuracy of measurement
Accuracy of age
Risks :
Exclude children who are small-for-age
Underestimate prevalence of stunting
Underestimate effect of the intervention
Population census at baseline :
Verify DOB from documents, if available
Event calendars to estimate age
Anaemia & Iron
Haemoglobin :
Easy to measure (finger prick blood)
Hemocue (easy to train, portable, battery operated)
Practical challenges – climate: dust / heat -> maintenance and type of photometer, 201 or 301+
WHO definition of anaemia, since 1958
Children aged 6-59 months:
Mild anaemia Hb< 110 g/lModerate anaemia Hb <80 g/lSevere anaemia Hb <50 g/l
Add photo
hemocue
Anaemia & Iron
Many causes of anaemia :
Iron deficiency
Vitamin A deficiency
other micronutrients Vit B12,C, folic acid, riboflavin
Inflammation & Infection malaria, hookworm, urinary & intestinal schistosomiasis
Inherited RBC disorders
Total population
Iron Deficiency
IrondeficiencyAnaemia
Anaemia
Anaemia Iron-deficiency
Anaemia & Iron
Other measures of iron status : Serum ferritin - marker of depleted iron stores
Transferrin, zinc protoprophyrin
Acute phase proteins (CRP, ACT, AGP) – markers of infection or inflammation
But: Multiple measures – larger blood volume Expert knowledge, Increased cost
WHO, 2007
Anaemia & Iron
Other measures of iron status : Serum ferritin – marker of depleted iron stores
Transferrin, zinc protoprophyrin
Acute phase proteins (CRP, ACT, AGP) – markers of infection or inflammation
But: Multiple measures – larger blood volume Expert knowledge, Increased cost
“Haemoglobin is a satisfactory indicator for measuring the effectiveness of a program, but lacks sensitivity when prevalence of anaemia is low”
WHO, 2007
• Focus on attention, memory, thinking and understanding – precursors to learning
• Known foundation skills for early literacy and numeracy
• Assessing information processing ability rather than learned knowledge
Physical health
•Nutrition & disease
Cognitive processing
•Thinking & processing ability
Learning
•Early literacy & mathematics
Cognitive foundation skills
Cognitive tests
TestCore skill /
domainFoundation skills
1) ExpressiveVocabulary
Spoken language / Executive function
Literacy and language
2) Oral Comprehension Language Literacy and language
3) Rapid automated naming (RAN): animals
Spoken language / Executive function
Literacy and numeracy
4) Digit-span Working memory Literacy and numeracy
5) Mosquitoes & ballsVisual search / Attention
Education outcomes
6) Heads-Shoulders-Knees-Toes (HSKT)
Executive function / Self regulation
Education outcomes
Cognitive tests
• Cognitive foundation skills for learning
• School-readiness
Thank you!
Acknowledgements
Malaria control in schools
Educational Attainment
Absent from
School
Reduced cognitive
performance
Malaria Infection in Schoolchildren
Clinical AttackAsymptomatic
Parasitaemia
Anaemia
Reduced attention
during lessons
Hypothesised relationship between malaria infection, cognition and education
Trials of intermittent parasite clearance in schools (IPCs)
?
Significant improvements in sustained attention have been recorded in two trials in two different transmission settings: Kenya and Mali
Trial in schools in Mali
% of
students
infected
May 2012: Control InterventionP. falciparum infection 74.8% 9.1% p<0.001Pf gametocytes 7.6% 0.8%Anaemia Hb<11g/dl 49.2% 35.8% p=0.003
0
20
40
60
80
100
Control
Intervention
Nov-10 Feb-12 May-12Nov-11
ITNs IPC parasite clearance
Impact on cognition
Cognitive testing in all 80 schools (1314 children in classes 4 and 5) found significant improvement in double digit test scores in the intervention group
February 2012
Summary Statistics Mean
Mean Crude Change from Baseline
Difference in change between baseline
and follow up P-valueControl Intervention Control Intervention
Single digit testz-score
1.39 1.34 + 1.32 + 1.41 + 0.09 (-0.05 to +0.21) 0.248
Double digit test
z-score0.37 0.53 + 0.34 + 0.57 + 0.23 (+0.10 to +0.36) 0.001
Effect size (95%CI): Single digit: 0.09 SD (-0.05 to 0.21)Double digit: 0.23 SD ( 0.10 to 0.36)
Adjusted for clustering within schools and repeated measures, age, sex and school class
Tests of sustained attention
All children resident in community eligible to receive interventions (community-wide distribution)
Fixed point delivery, MSF model
ECCD centre as a rallying point – sensitization, training, distribution
Community responsible for administering interventions
Managed through existing school and ECCD management structures
Community-led, ECCD-centred
Checking age eligibility SMC treatment Observation post-treatment
Community-led, ECCD-centred
Seasonal
malaria
chemoprevention
Sikasso, Mali
Training of ECCD staff/women’s group leaders
– Good nutrition practices for early childhood
– How to use micronutrient powders (MNPs)
Cooking demonstrations in village by women’s groups
Delivery of MNPs to ECCD centres
Distribution of MNPs to households
Nutrition