Malaria prevention with nutrient supplementation in addition to seasonal chemoprevention in children aged 6-59 months in rural Mali

1 University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team IDLIC, UMR 1219, Bordeaux, France2 University of Zinder, Faculty of Medicine, Zinder, Niger3 The Alliance for International Medical Action (ALIMA), Dakar, Senegal4 ALIMA/Alliance Médicale Contre le Paludisme (AMCP), Bamako, Mali

anne.thomas@u-bordeaux.fr

RN

7

aban-coro

BAMAKO

BenBougoucoura

Dankorofougan

DossorolaFanflebougou

Fougan

Kaouena

Kofougan

N'goloblembougo

N'golobougou

Sabougou

Somambougou

Bilissabougou

Bougoudiana

BouloukoumaDjiribabougou

Finkessiyoro

Kena

Kossoumale

Markala

Messa

Monitiala

Nantoumana

Ngabakorodansine

Nokala

Ouolodiedo

Sikorononkon

Tieneguebougou

Tienko

Bafebougou

Diarabougou

urako

a

Forokobougou

Kabana 2

Kenekolo

Kodian

Mintiguila

Mpolona

ugou

NgolobougouOuarala

Pintierebougou

mon Tamanisoba

Tenezana

TienkoulaZambougou

Dababougou

Dani

Diekouma

Djeguebougou

N'tjila

omodo

Ngabakorotresain

Sanadie

go

Dassombougou

Diamandi

Doribougou

Kaneguebougou

Niara

o

Sirakoro

Sominebougou

BOUGOU

OUOLODO

NONSSOMBOUGOU

NONKON

KOULIKORO

Source(s):Données spatiales: DNCT, DNP, INSTAT,

Cluster Logistique, UNCS

Avertissements:Les Nations Unies ne sauraient être tenuesresponsables de la qualité des limites, des noms etdes désignations utilisés sur cette carte

1:650 000

OCHA KOULIKORO KOLOKANI A3 20131010

Octobre 2013

GCS/WGS 84

https://mali.humanitarianresponse.info

Nom de la carte:

Date de création:

Projection/Datum:

Web :

Echelle nominale sur papier A3 :

MAURITANIE

ALGERIE

NIGER

GUINEE

BURKINA FASO

SE

NE

GA

L

0 2512,5 Km

INTRODUCTION • In Mali, in children <5 years old: mortality rate estimated at 115 per 1,000 live births, 20-24% of these deaths caused by malaria (2015 estimate, World Health Statistics, 2016)

• Prevalence of moderate acute malnutrition (MAM) and severe acute malnutrition (SAM) in children <5 years old in 2016, measured by weight-for-height Z-score: 8.6% [7.6–9.7] and 2.1% [1.7–2.5], respectively (Mali SMART survey, 2016)

• Malaria and malnutrition: complex link and similar seasonality in Mali

• No published large-scale trials on impact of seasonal malaria chemoprevention (SMC) / lipid-based nutrient supplement (LNS) joint distribution in sub-Saharan Africa

To determine whether concurrent distribution of SMC and LNS reduces the occurrence of malaria episodes when compared to use of SMC alone among children aged 6-59 months

METHOD

• A paired cluster cohort study carried out between August and November 2016 in 18 rural health areas of Kolokani Circle, Koulikoro region, Mali• Health areas matched by estimated under-five year child population in 2016 and their geographic localization in Kolokani Circle (north or south)

• Verification of community health worker compliance to the malaria RDT protocol• Intention to treat (ITT) and per protocol (PP) analyses; PP analysis only included children who attended all 4 rounds of SMC distribution• Generalized linear mixed models with study teams and individuals as nested random effects

RESULTS

AnalysesOutcomes

Population

Study design

• Children aged 6-59 months participating in community-based SMC distribution sessions

• Primary outcome: occurrence of malaria episodes defined by a positive rapid diagnostic test (RDT), detected from the 2nd through the 4th round• Secondary outcome: occurrence of a repeated malaria episode in the 3rd or 4th round among children who have had a first malaria episode in the 2nd or 3rd round

Association between the intervention and the occurrence of repeated malaria episodes

CONCLUSION

• No impact of the intervention on the occurrence of malaria episodes but reduction of the risk of repeated malaria episodes

• First study on combined SMC/LNS distribution on a large scale

• Cooperation of national health and political actors, humanitarian NGOs and researchers

• Need for more robust studies including randomization, additional data on mosquito nets and LNS effective consumption, assessment of malaria cases at 4th round

Intervention

Round 1Aug.

Round 2 Round 3 Round 4Nov.Oct.Sept.

4 weeks 5 weeks 5 weeks

SMC SMC SMC SMC

SMC+LNS SMC+LNS SMC+LNS SMC+LNS

Control group

Intervention group

SMC= a treatment of sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ)• 3 doses during 3 consecutive days: D1: SP+AQ at distribution site D2 & D3: AQ at home• 2 dosage categories according to age: 6-11 months: SP 250mg/12.5mg and AQ 75mg 12-59 months: SP 500mg/25mg and AQ 150mg

LNS= lipid-based nutrient supplement to prevent malnutrition, 50g or 250kcal per sachet (medium quantity)• 2 dosage categories according to age: 6-11 months: 15 sachets/month or 50g every two days for 4 weeks 12-59 months: 21 sachets/month or 50g per day for 3 weeks

History of fever in the last 48 hours OR axillary temperature ≥ 37.5°C

RDT for malaria parasites based on histidine-rich protein II

Malaria RDT protocol

No association between the intervention and the occurrence of malaria episodes1

2

* Total number of observations; ** Percentage of confirmed malaria episodes on total number of observations; *** odds ratio adjusted for sex, age, global acute malnutrition at the previous round, enrollment in nutritional program at current round, confirmed malaria at 1st round, round number, SMC distribution site, geographic localization

Intention to treat analysis Per protocol analysis

Nobs* Nobs*%** %**aOR*** aOR***95% CI 95% CIp value p value

Group

SMC

SMC+LNS

25,21130,051

20,809

9,242

7.08

7.03

1

0.97

Ref

[0.67–1.41]

0.830.89

[0.68–1.36]0.96

1 Ref

7.10

7.1217,298

7,913

* Number of children who have had a confirmed malaria episode at 2nd or 3rd round; ** Percentage of children who have had a second confirmed malaria episode at 3rd or 4th round, among children who have had a first confirmed malaria episode at 2nd or 3rd round; *** odds ratio adjusted for sex, age, confirmed malaria at 1st round, SMC distribution site, geographic localization

Intention to treat analysis Per protocol analysis

N* N*%** %**aOR*** aOR***95% CI 95% CIp value p value

Group

SMC

SMC+LNS

1,1591,424

985

439

16.75

10.48

1

0.55

Ref

[0.35–0.87]

<0.0010.01

[0.28–0.69]0.44

1 Ref

11.62

19.77789

370

Anne THOMAS , Mahamadou DOUTCHI , Abdelkader ISSALEY , Issa KANTA , Maguy DAURES , Ali OUATTARA , Susan SHEPHERD , Renaud BECQUET

1

1 1

2 3

3 3

4

Number of children recorded in databasen= 38,452

No respect of age limit; n= 1,735

Number of children aged 6-59 months in 18 health areas involved in the study

n= 36,717

Exclusion of teams with poor protocol compliance, e.g. more than 5% of missing data for the variables “temperature” and “fever antecedent”, and with less than 85% of actually realized RDTs when expected in rounds 2, 3 and 4; n= 25,051

Control group(8 health areas)

Intervention group(6 health areas)

Number of children at 1st roundn= 8,158

Number of children at 1st roundn= 3,508

Number of children at 2nd roundn= 7,414 (90.9%)*

Number of children at 2nd roundn= 3,294 (93.9%)*

Number of children at 3rd roundn= 7,139 (87.5%)*

Number of children at 3rd roundn= 3,117 (88.9%)*

Number of children at 4th roundn= 6,451 (79.1%)*

Number of children at 4th roundn= 2,972 (84.7%)*

* Percentage of children who came back compared to the number of children enrolled for the 1st round

Number of children who attended all 4 rounds

n= 2,678 (76.3%)*

Number of children who attended all 4 rounds

n= 5,819 (71.3%)*

Flow chart of children eligible for the analysis

Number of children aged 6-59 months eligible for analysis

n= 11,666

ITT population PP population