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

0.000

0.100

0.200

0.300

0.400

0.500

0.600

0.700

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