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Cochrane Database of Systematic Reviews

Mass drug administration for malaria

Information

DOI:
https://doi.org/10.1002/14651858.CD008846.pub3Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 29 September 2021see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:

  1. Cochrane Infectious Diseases Group

Copyright:
  1. Copyright © 2021 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.
  2. This is an open access article under the terms of the Creative Commons Attribution-Non-Commercial Licence , which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Authors

  • Monica P Shah

    Correspondence to: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, USA

    [email protected]

  • Jimee Hwang

    U.S. President’s Malaria Initiative, Malaria Branch, Centers for Disease Control and Prevention, Atlanta, USA

    Global Health Group, University of California San Francisco, San Francisco, USA

  • Leslie Choi

    Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK

  • Kim A Lindblade

    Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, USA

  • S Patrick Kachur

    Department of Population and Family Health, Columbia University Medical Center, New York, USA

  • Meghna Desai

    Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, USA

Contributions of authors

MD, JH, SPK, and KAL conceived of and designed the protocol. MPS and MD reviewed the literature and extracted the data. KAL and LC helped to resolve discrepancies. MPS, LC, and MD conducted the analyses. MPS, LC, and MD drafted the manuscript. All authors reviewed and provided final approval of the manuscript prior to publication.

Sources of support

Internal sources

  • Centers for Disease Control and Prevention, USA

  • US President's Malaria Initiative, USA

    JH received salary support

  • Liverpool School of Tropical Medicine, UK

External sources

  • Foreign, Commonwealth and Development Office (FCDO), UK

    Project number 300342‐104

Declarations of interest

MPS has no known conflicts of interest.

JH has no known conflicts of interest.

LC has no known conflicts of interest.

KAL has no known conflicts of interest.

SPK has no known conflicts of interest.

MD has no known conflicts of interest.

Acknowledgements

The Academic Editor is Dr Joseph Okebe.

The editorial base of the Cochrane Infectious Diseases Group is funded by UK aid from the UK government for the benefit of low‐ and middle‐income countries (project number 300342‐104). The views expressed do not necessarily reflect the UK government’s official policies.

We thank Marty Chaplin, Statistical Editor with the Cochrane Infectious Diseases Group (CIDG), for the statistical advice provided in this review. We also appreciate the assistance of Vittoria Lutje, CIDG Information Specialist, for running the literature search strategy.

Leslie Choi is supported by the Research, Evidence and Development Initiative (READ‐It) project. READ‐It (project number 300342‐104) is funded by UK aid from the UK government; however, the views expressed in this review do not necessarily reflect the UK government’s official policies. 

Jimee Hwang receives salary support from the US President's Malaria Initiative.

We acknowledge Dr Thom Eisele, Dr Alistair McLean, and Dr Ulrika Morris for sharing unpublished data from their trials and also for their permission to include these data in the review in preparation for the WHO Evidence Review Group meeting on MDA for malaria in September 2018. We also received assistance from Dr Lorenz von Seidlein regarding study clarifications.

Version history

Published

Title

Stage

Authors

Version

2021 Sep 29

Mass drug administration for malaria

Review

Monica P Shah, Jimee Hwang, Leslie Choi, Kim A Lindblade, S Patrick Kachur, Meghna Desai

https://doi.org/10.1002/14651858.CD008846.pub3

2013 Dec 09

Mass drug administration for malaria

Review

Eugenie Poirot, Jacek Skarbinski, David Sinclair, S Patrick Kachur, Laurence Slutsker, Jimee Hwang

https://doi.org/10.1002/14651858.CD008846.pub2

2010 Nov 10

Mass drug administration for malaria

Protocol

Eugenie Poirot, Jimee Hwang, S Patrick Kachur, Laurence Slutsker, Jacek Skarbinski

https://doi.org/10.1002/14651858.CD008846

Differences between protocol and review

Differences between review and review update

A new author team was formed for this 2021 review update, with several authors from the previous review version (JH, SPK). Dr Monica Shah is the contact author for this 2021 review update.

Pre‐specified revisions made to the background, inclusion criteria, and methods sections are detailed in Appendix 2. In addition, we analysed non‐randomized studies using a difference‐in‐difference analysis, as detailed in the methods section of this review update. We also conducted a post‐hoc analysis to explore differences in malaria epidemiology by continent as a reason for heterogeneity in effect of MDA on P falciparum parasitaemia prevalence at one to three months after MDA in very low‐ to low‐endemicity settings. The post‐hoc analysis by subgroup (studies conducted in Africa and Asia) is presented in Analysis 4.1.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Humans;

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram

Figures and Tables -
Figure 1

Study flow diagram

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Risk of bias summary: review authors' judgements about each risk of bias item for each included study

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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

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Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

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Comparison 1: MDA versus no MDA in moderate to high endemicity (cRCTs) on P falciparum outcomes, Outcome 1: Parasitaemia prevalence (P falciparum)

Figures and Tables -
Analysis 1.1

Comparison 1: MDA versus no MDA in moderate to high endemicity (cRCTs) on P falciparum outcomes, Outcome 1: Parasitaemia prevalence (P falciparum)

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Comparison 1: MDA versus no MDA in moderate to high endemicity (cRCTs) on P falciparum outcomes, Outcome 2: Parasitaemia incidence (P falciparum)

Figures and Tables -
Analysis 1.2

Comparison 1: MDA versus no MDA in moderate to high endemicity (cRCTs) on P falciparum outcomes, Outcome 2: Parasitaemia incidence (P falciparum)

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Comparison 1: MDA versus no MDA in moderate to high endemicity (cRCTs) on P falciparum outcomes, Outcome 3: Confirmed malaria illness incidence (P falciparum)

Figures and Tables -
Analysis 1.3

Comparison 1: MDA versus no MDA in moderate to high endemicity (cRCTs) on P falciparum outcomes, Outcome 3: Confirmed malaria illness incidence (P falciparum)

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Comparison 1: MDA versus no MDA in moderate to high endemicity (cRCTs) on P falciparum outcomes, Outcome 4: Gametocytaemia prevalence (P falciparum)

Figures and Tables -
Analysis 1.4

Comparison 1: MDA versus no MDA in moderate to high endemicity (cRCTs) on P falciparum outcomes, Outcome 4: Gametocytaemia prevalence (P falciparum)

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Comparison 1: MDA versus no MDA in moderate to high endemicity (cRCTs) on P falciparum outcomes, Outcome 5: Malaria‐specific mortality

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Analysis 1.5

Comparison 1: MDA versus no MDA in moderate to high endemicity (cRCTs) on P falciparum outcomes, Outcome 5: Malaria‐specific mortality

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Comparison 2: MDA versus no MDA in very low to low endemicity (cRCTs) on P falciparum outcomes, Outcome 1: Parasitaemia prevalence (P falciparum)

Figures and Tables -
Analysis 2.1

Comparison 2: MDA versus no MDA in very low to low endemicity (cRCTs) on P falciparum outcomes, Outcome 1: Parasitaemia prevalence (P falciparum)

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Comparison 2: MDA versus no MDA in very low to low endemicity (cRCTs) on P falciparum outcomes, Outcome 2: Parasitaemia incidence (P falciparum)

Figures and Tables -
Analysis 2.2

Comparison 2: MDA versus no MDA in very low to low endemicity (cRCTs) on P falciparum outcomes, Outcome 2: Parasitaemia incidence (P falciparum)

Navigate to figure in ReviewOpen in new tab

Comparison 2: MDA versus no MDA in very low to low endemicity (cRCTs) on P falciparum outcomes, Outcome 3: Confirmed malaria illness incidence (P falciparum)

Figures and Tables -
Analysis 2.3

Comparison 2: MDA versus no MDA in very low to low endemicity (cRCTs) on P falciparum outcomes, Outcome 3: Confirmed malaria illness incidence (P falciparum)

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Comparison 3: MDA versus no MDA in very low to low endemicity (cRCTs) on P vivax outcomes, Outcome 1: Parasitaemia prevalence (P vivax)

Figures and Tables -
Analysis 3.1

Comparison 3: MDA versus no MDA in very low to low endemicity (cRCTs) on P vivax outcomes, Outcome 1: Parasitaemia prevalence (P vivax)

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Comparison 3: MDA versus no MDA in very low to low endemicity (cRCTs) on P vivax outcomes, Outcome 2: Confirmed malaria illness incidence (P vivax)

Figures and Tables -
Analysis 3.2

Comparison 3: MDA versus no MDA in very low to low endemicity (cRCTs) on P vivax outcomes, Outcome 2: Confirmed malaria illness incidence (P vivax)

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Comparison 4: Supplemental analysis: post‐hoc subgroup analysis by continent, Outcome 1: Plasmodium falciparum parasitaemia prevalence post‐MDA 1‐3 months

Figures and Tables -
Analysis 4.1

Comparison 4: Supplemental analysis: post‐hoc subgroup analysis by continent, Outcome 1: Plasmodium falciparum parasitaemia prevalence post‐MDA 1‐3 months

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Summary of findings 1. MDA compared to no MDA for Plasmodium falciparum malaria (moderate to high endemicity, short‐term follow‐up)

Patient or population: People of all ages living in an area with moderate to high endemicity of P falciparum malaria (≥ 10% prevalence)
Setting: Moderate to high endemicity defined as ≥10% prevalence of P falciparum
Intervention: MDA
Comparison: Control (no MDA or placebo)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with no MDA

Risk with MDA

Follow‐up: 1 to 3 months

Parasitaemia prevalence

5 per 100

9 per 100
(3 to 27)

RR 1.76
(0.58 to 5.36)

786
(1 RCT)

⊕⊕⊝⊝
LOWa,b,c

Due to imprecision

At 1‐3 months post‐MDA, parasite prevalence may increase in MDA compared no MDA. However, the effects vary and it is possible that MDA makes little or no difference on parasitaemia prevalence.

Parasitaemia incidence

68 events per 100 person‐years

42 events per 100 person‐years
(27 to 63)

Rate ratio 0.61
(0.40 to 0.92)

739
(1 RCT)

⊕⊕⊕⊝
MODERATEa,b,d

Due to imprecision

At 1‐3 months post‐MDA, there is probably a reduction in parasitaemia incidence in MDA compared to no MDA.

Confirmed malaria illness incidence

28 per 1000 population

11 per 1000 population
(1 to 122)

Rate ratio 0.41
(0.04 to 4.42)

144,422
(1 RCT)

⊕⊕⊝⊝
LOWa,b,c

Due to imprecision

At 1‐3 months post‐MDA, there may be a reduction in confirmed malaria illness incidence in MDA compared to no MDA.

Follow‐up: 4 to 6 months

Parasitaemia prevalence

55 per 100

65 per 100
(49 to 86)

RR 1.18
(0.89 to 1.56)

1414
(1 RCT)

⊕⊕⊕⊝
MODERATEa,b,d

Due to imprecision

At 4‐6 months post‐MDA, there is probably little or no effect on parasitaemia prevalence in MDA compared to no MDA

Parasitaemia incidence

129 events per 100 person‐years

118 events per 100 person‐years
(71 to 194)

Rate ratio 0.91
(0.55 to 1.50)

1376
(1 RCT)

⊕⊝⊝⊝
VERY LOWa,b,d,e

Due to risk of bias and imprecision

We do not know if MDA has an effect on parasitaemia incidence at 4‐6 months post‐MDA

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; cRCT: cluster‐randomized controlled trial; MDA: mass drug administration; RCT: randomized controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

aNot downgraded for inconsistency; the comparison presented is reported from a single study.
bNot downgraded for indirectness; outcome was evaluated in all ages or assessed in children (considered the most appropriate population to measure malaria transmission in moderate‐ to high‐endemicity areas).
cDowngraded 2 levels for imprecision due to very wide CIs.
dDowngraded 1 level for imprecision due to wide CIs.
eDowngraded 2 levels for risk of bias since malaria cases in outcome were defined as fever plus parasitaemia > 5000, which excludes all afebrile and low density infections and results in an underestimate of the outcome.

Figures and Tables -
Summary of findings 1. MDA compared to no MDA for Plasmodium falciparum malaria (moderate to high endemicity, short‐term follow‐up)
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Summary of findings 2. MDA compared to no MDA for Plasmodium falciparum malaria (very low to low endemicity, short‐term follow‐up)

Patient or population: People of all ages living in an area with very low to low endemicity of P falciparum malaria (< 10% prevalence)
Setting: Very low to low endemicity defined as < 10% prevalence of P falciparum
Intervention: MDA
Comparison: Control (no MDA or placebo)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with Control

Risk with MDA

Follow‐up: < 1 month

Parasitaemia prevalence
follow up: range < 1 month

12 per 100

1 per 100
(0 to 6)

RR 0.12
(0.03 to 0.52)

1232
(1 RCT)

⊕⊕⊝⊝
LOWa‐d

Due to risk of bias and imprecision

At < 1 month post‐MDA, there may a reduction in parasitaemia prevalence in MDA compared to no MDA.

Follow‐up: 1 to 3 months

Parasitaemia prevalence

3 per 100

1 per 100

(0 to 1)

RR: 0.25

(0.15 to 0.41)

17,454
(7 RCTs)5

⊕⊕⊝⊝
LOWe‐i

Due to risk of bias

At 1‐3 months post‐MDA, there may a reduction in parasitaemia prevalence in MDA compared to no MDA.

Parasitaemia incidence

15 events per 100 person‐years

5 events per 100 person‐years
(3 to 10)

Rate ratio 0.37
(0.21 to 0.66)

736
(1 RCT)

⊕⊕⊕⊝
MODERATEb,d,,j

Due to imprecision

At 1‐3 months post‐MDA, there is probably a reduction in parasitaemia incidence in MDA compared to no MDA.

Confirmed malaria illness incidence

6 per 1000 population

4 per 1000 population
(1 to 17)

Rate ratio: 0.58

(0.12 to 2.73)

130,651
(2 RCTs)

⊕⊝⊝⊝
VERY LOWa,j‐l

Due to risk of bias and imprecision

We do not know if MDA has an effect on confirmed malaria illness incidence at 1‐3 months post‐MDA compared to no MDA.

Follow‐up: 4 to 6 months

Parasitaemia prevalence

5 per 100

3 per 100

(2 to 6)

RR: 0.63

(0.36 to 1.12)

5670

(4 RCTs)

⊕⊝⊝⊝
VERY LOWc,d,f,l

Due to risk of bias and imprecision

We do not know if MDA has an effect on parasitaemia prevalence at 4‐6 months post‐MDA compared to no MDA.

 

Confirmed malaria illness incidence

4 per 1000 population

4 per 1000 population
(0 to 53)

Rate ratio 0.93
(0.07 to 12.43)

23,251
(1 RCT)

⊕⊝⊝⊝
VERY LOWa,b,k,l

Due to risk of bias and imprecision

We do not know if MDA has an effect on confirmed malaria illness incidence at 4‐6 months post‐MDA compared to no MDA.

Follow‐up: 7 to 12 months

Parasitaemia prevalence

5 per 100

4 per 100

(3 to 6)

RR: 0.86

(0.55 to 1.36)

7760

(5 RCTs)

⊕⊝⊝⊝
VERY LOWc,d,l,m

Due to risk of bias and imprecision

We do not know if MDA has an effect on parasitaemia prevalence at 7‐12 months post‐MDA compared to no MDA.

Confirmed malaria illness incidence

11 per 1000 population

5 per 1000 population (2 to 12)

Rate ratio 0.47

(0.21 to 1.03)

26,576
(3 RCTs)

⊕⊝⊝⊝
VERY LOWd,f,j,l

Due to risk of bias and imprecision

We do not know if MDA has an effect on confirmed malaria illness incidence at 7‐12 months post‐MDA compared to no MDA.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; cRCT: cluster‐randomized controlled trial; MDA: mass drug administration; RCT: randomized controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

aDowngraded 1 level for risk of bias due to several criteria scored as high or unclear risk of bias.
bNot downgraded for inconsistency; the comparison presented is reported from a single study.
cNot downgraded for indirectness; all ages are at similar risk of malaria transmission, given the local epidemiology of malaria in this study setting and the outcomes were assessed by a highly sensitive diagnostic method (ultrasensitive PCR).
dDowngraded 1 level for imprecision due to wide CIs.
eEight included studies reported parasitaemia prevalence during the 1‐3 month post‐MDA follow‐up period; however, one study did not contribute data in the meta‐analysis due to no events at baseline before MDA or at any follow‐up time points.
fDowngraded 2 levels for risk of bias due to several criteria scored as high or unclear risk of bias, including baseline imbalance and high risk of contamination in several studies.
gNot downgraded for inconsistency based on I2 statistic; however, reasons for heterogeneity explored in post‐hoc sub‐group analysis by continent (sub‐Saharan Africa and Southeast Asia; Analysis 4.1).
hNot downgraded for indirectness; all ages are at similar risk of malaria transmission, given the local epidemiology of malaria in this study setting so there is no concern with assessing this outcome in different age groups across studies.
iNot downgraded for imprecision due to appreciable benefit of pooled effect as reported by seven studies.
jNot downgraded for indirectness since outcome was assessed in all ages and by routine detection methods.
kDowngraded 2 levels for imprecision due to very wide CIs.
lNot downgraded for inconsistency based on I2 statistic.
mDowngraded 2 levels for risk of bias due to several criteria scored as high or unclear risk of bias, including baseline imbalance, high risk of contamination, and a large unexplained increase in sampled population in the MDA group at this time point.
 

Figures and Tables -
Summary of findings 2. MDA compared to no MDA for Plasmodium falciparum malaria (very low to low endemicity, short‐term follow‐up)
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Summary of findings 3. MDA compared to no MDA for Plasmodium falciparum malaria (very low to low endemicity, long‐term follow‐up)

Patient or population: People of all ages living in an area with very low to low endemicity of P falciparum malaria ( < 10% prevalence)
Setting: Very low to low endemicity defined as < 10% prevalence of P falciparum
Intervention: MDA
Comparison: Control (no MDA or placebo)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with Control

Risk with MDA

Follow‐up: 13 to 18 months

Parasitaemia prevalence

4 per 100

4 per 100
(1 to 14)

RR 0.82
(0.20 to 3.34)

1537
(1 RCT)

⊕⊝⊝⊝
VERY LOWa‐d

Due to risk of bias and imprecision

We do not know if MDA has an effect on parasitaemia prevalence at 13‐18 months post‐MDA compared to no MDA.

Confirmed malaria illness incidence

17 per 1000 population

13 per 1000 population
(3 to 51)

Rate ratio 0.77
(0.20 to 3.03)

23,251
(1 RCT)

⊕⊝⊝⊝
VERY LOWb,d‐f

Due to risk of bias and imprecision

We do not know if MDA has an effect on confirmed malaria illness incidence at 13‐18 months post‐MDA compared to no MDA.

Follow‐up: 19 to 24 months

Parasitaemia prevalence
follow‐up: range 19 to 24 months

3 per 100

1 per 100
(0 to 6)

RR 0.34
(0.06 to 1.97)

1393
(1 RCT)

⊕⊝⊝⊝
VERY LOWa‐d

Due to risk of bias and imprecision

We do not know if MDA has an effect on parasitaemia prevalence at 19‐24 months post‐MDA compared to no MDA.

Follow‐up: 25 months and above

Parasitaemia prevalence
follow‐up: range 25 to 30 months

3 per 100

3 per 100
(1 to 12)

RR 0.89
(0.22 to 3.62)

1521
(1 RCT)

⊕⊝⊝⊝
VERY LOWa‐d

Due to risk of bias and imprecision

We do not know if MDA has an effect on parasitaemia prevalence at 25‐30 months post‐MDA compared to no MDA.

Parasitaemia prevalence
follow‐up: range 31 to 36 months

3 per 100

4 per 100
(1 to 19)

RR 1.25
(0.25 to 6.31)

1679
(1 RCT)

⊕⊝⊝⊝
VERY LOWa‐d

Due to risk of bias and imprecision

We do not know if MDA has an effect on parasitaemia prevalence at 31‐36 months post‐MDA compared to no MDA.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; cRCT: cluster‐randomized controlled trial; MDA: mass drug administration; RCT: randomized controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

aDowngraded 2 levels for risk of bias due to several criteria scored as high or unclear risk of bias, including baseline imbalance, high risk of contamination, and a large unexplained increase in sampled population in the MDA group at this time point.
bNot downgraded for inconsistency; the comparison presented is reported from a single study.
cNot downgraded for indirectness; all ages are at similar risk of malaria transmission, given the local epidemiology of malaria in this study setting and the outcomes were assessed by a highly sensitive diagnostic method (ultrasensitive PCR).
dDowngraded 2 levels for imprecision due to very wide CIs.
eDowngraded 1 level for risk of bias due to several criteria scored as high or unclear risk of bias.
fNot downgraded for indirectness since outcome was assessed in all ages and by routine detection methods.

Figures and Tables -
Summary of findings 3. MDA compared to no MDA for Plasmodium falciparum malaria (very low to low endemicity, long‐term follow‐up)
Navigate to table in Review
Summary of findings 4. MDA compared to no MDA for P vivax malaria (very low to low endemicity, short‐term follow‐up)

Patient or population: People of all ages living in an area with very low to low endemicity of P vivax malaria (< 10% prevalence)
Setting: Very low to low endemicity defined as < 10% prevalence of P vivax
Intervention: MDA
Comparison: Control (no MDA or placebo)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with Control

Risk with MDA

Follow‐up: < 1 month

Parasitaemia prevalence
follow up: range < 1 month

27 per 100

5 per 100
(2 to 11)

RR 0.18
(0.08 to 0.40)

1232
(1 RCT)

⊕⊕⊝⊝
LOWa‐d

Due to risk of bias and imprecision

At < 1 month post‐MDA, there may a reduction in parasitaemia prevalence in MDA compared to no MDA.

Follow‐up: 1 to 3 months

Parasitaemia prevalence

12 per 100

2 per 100

(1 to 3)

RR: 0.15

(0.10 to 0.24)

6896

(5 RCTs)

⊕⊕⊝⊝
LOWc,e‐g

Due to risk of bias

At 1‐3 months post‐MDA, there may a reduction in parasitaemia prevalence in MDA compared to no MDA.

Follow‐up: 4 to 6 months

Parasitaemia prevalence

11 per 100

9 per 100

(7 to 10)

RR: 0.78

(0.63 to 0.95)

 

5670

(4 RCTs)

⊕⊝⊝⊝
VERY LOWc,d,f,h

Due to risk of bias and imprecision

We do not know if MDA reduces parasitaemia prevalence at 4‐6 months post‐MDA compared to no MDA.

Follow‐up: 7 to 12 months

Parasitaemia prevalence

9 per 100

11 per 100

(9 to 13)

RR: 1.12

(0.94 to 1.34)

7760

(5 RCTs)

⊕⊝⊝⊝
VERY LOWc,d,h,i

Due to risk of bias and imprecision

We do not know if MDA has an effect on parasitaemia prevalence at 7‐12 months post‐MDA compared to no MDA.

Confirmed malaria illness incidence

41 per 1000 population

57 per 1000 population (40 to 80)

Rate ratio: 1.38

(0.97 to 1.95)

3325

(2 RCTs)

⊕⊝⊝⊝
VERY LOWd,f,h,j

Due to risk of bias and imprecision

We do not know if MDA has an effect on confirmed malaria illness incidence at 7‐12 months post‐MDA compared to no MDA.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; cRCT: cluster‐randomized controlled trial; MDA: mass drug administration; RCT: randomized controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

aDowngraded 1 level for risk of bias due to several criteria scored as high or unclear risk of bias.
bNot downgraded for inconsistency; the comparison presented is reported from a single study.
cNot downgraded for indirectness; all ages are at similar risk of malaria transmission, given the local epidemiology of malaria in this study setting and the outcomes were assessed by a highly sensitive diagnostic method (ultrasensitive PCR).
dDowngraded 1 level for imprecision due to wide CIs.
eNot downgraded for imprecision due to appreciable benefit of pooled effect as reported by five studies.
fDowngraded 2 levels for risk of bias due to several criteria scored as high or unclear risk of bias, including baseline imbalance and high risk of contamination.
gNot downgraded for inconsistency despite the large value of the I2 statistic since the direction of effect was consistent with large imprecision.
hNot downgraded for inconsistency based on I2 statistic.
iDowngraded 2 levels for risk of bias due to several criteria scored as high or unclear risk of bias, including a large unexplained increase in sampled population in the MDA group at this time point.
jNot downgraded for indirectness since outcome was assessed in all ages and by routine detection methods.

Figures and Tables -
Summary of findings 4. MDA compared to no MDA for P vivax malaria (very low to low endemicity, short‐term follow‐up)
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Summary of findings 5. MDA compared to no MDA for P vivax malaria (very low to low endemicity, long‐term follow‐up)

Patient or population: People of all ages living in an area with very low to low endemicity of P vivax malaria (< 10% prevalence)
Setting: Very low to low endemicity < 10% prevalence of P vivax
Intervention: MDA
Comparison: Control (no MDA or placebo)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with Control

Risk with MDA

Follow‐up: 13 to 18 months

Parasitaemia prevalence

17 per 100

14 per 100
(8 to 25)

RR 0.81
(0.44 to 1.48)

1537
(1 RCT)

⊕⊝⊝⊝
VERY LOWa‐d

Due to risk of bias and imprecision

We do not know if MDA reduces parasitaemia prevalence at 13‐18 months post‐MDA compared to no MDA.

Follow‐up: 19 to 24 months

Parasitaemia prevalence
follow‐up: range 19 to 24 months

11 per 100

9 per 100
(4 to 20)

RR 0.84
(0.38 to 1.83)

1393
(1 RCT)

⊕⊝⊝⊝
VERY LOWa‐d

Due to risk of bias and imprecision

We do not know if MDA reduces parasitaemia prevalence at 19‐24 months post‐MDA compared to no MDA.

Follow‐up: 25 months and above

Parasitaemia prevalence
follow‐up: range 25 to 30 months

11 per 100

9 per 100
(4 to 21)

RR 0.89
(0.41 to 1.94)

1521
(1 RCT)

⊕⊝⊝⊝
VERY LOWa‐d

Due to risk of bias and imprecision

We do not know if MDA reduces parasitaemia prevalence at 25‐30 months post‐MDA compared to no MDA.

Parasitaemia prevalence
follow‐up: range 31 to 36 months

6 per 100

7 per 100
(3 to 20)

RR 1.20
(0.44 to 3.29)

1679
(1 RCT)

⊕⊝⊝⊝
VERY LOWa‐c,e

Due to risk of bias and imprecision

We do not know if MDA reduces parasitaemia prevalence at 31‐36 months post‐MDA compared to no MDA.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; cRCT: cluster‐randomized controlled trial; MDA: mass drug administration; RCT: randomized controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

aDowngraded 2 levels for risk of bias due to several criteria scored as high or unclear risk of bias, including a large unexplained increase in sampled population in the MDA group at this time point.
bNot downgraded for inconsistency; the comparison presented is reported from a single study.
cNot downgraded for indirectness; all ages are at similar risk of malaria transmission, given the local epidemiology of malaria in this study setting and the outcomes were assessed by a highly sensitive diagnostic method (ultrasensitive PCR).
dDowngraded 1 level for imprecision due to wide CIs.
eDowngraded 2 levels for imprecision due to very wide CIs.

Figures and Tables -
Summary of findings 5. MDA compared to no MDA for P vivax malaria (very low to low endemicity, long‐term follow‐up)
Navigate to table in Review
Table 1. Description of studies

Study ID (Design)

Year(s) of study

Malaria endemicitya

Plasmodium species

Antimalarial drug resistance

MDA group

Control group

Co‐intervention(s)b

Outcomes reported (months of follow‐up post‐MDAc)

Drug

Rounds, interval, and duration implemented

Population targeted (coverage)

Eisele 2020 ZMBa (cRCT)

2014‐2017

Low

P falciparum

Widespread resistance to CQ and SP, but no evidence of resistance to artemisinin

DHAp

4 rounds administered at start of rainy season, during rainy season, during dry season, and at start of rainy season over 15 months

37,694

(79% in round 1; 63% in round 2; 76% in round 3; 66% in round 4)

No drug and no placebo

IRS, ITNs, and enhanced standard of care

  • Parasitaemia prevalence (2)

  • Parasitaemia incidence (2)

  • Confirmed malaria case incidence (2)

  • Adverse effects

Eisele 2020 ZMBb (cRCT)

2014‐2017

High

P falciparum

Widespread resistance to CQ and SP, but no evidence of resistance to artemisinin

DHAp

4 rounds administered at start of rainy season, during rainy season, during dry season, and at start of rainy season over 15 months

45,442

(79% in round 1; 63% in round 2; 76% in round 3; 66% in round 4)

No drug and no placebo

IRS, ITNs, and enhanced standard of care

  • Parasitaemia prevalence (2)

  • Parasitaemia incidence (2)

  • Confirmed malaria case incidence (2)

  • Adverse effects

Escudie 1962 BFA (CBA)

1960‐1961

High

P falciparum,

P ovale,

P malariae

ND

AQ‐PQ or CQ‐PQ

(Low frequency MDA)

7 rounds administered 28 days apart over 7 months

1890

(75% to 91% per round)

No drug and no placebo

None (IRS arms excluded)

  • Parasitaemia prevalence (3)

  • Gametocytaemia prevalence (3)

(High frequency MDA)

15 rounds administered 14 days apart over 7 months

2560

(84% to 97% per round)

  • Parasitaemia prevalence (3)

  • Gametocytaemia prevalence (3)

Landier 2017 MMRa (cRCT)

2013‐2015

Low

P falciparum,

P vivax

Artemisinin resistance firmly established

DHAp with PQ

3 rounds administered 1 month apart over 3 months

1434 (66% in round 1, 56% in round 2, and 65% in round 3)

Delayed MDA

ITNs, uninterrupted access to case management

  • Parasitaemia prevalence (7)

  • Confirmed malaria illness incidence (7)

  • Adverse effects

McLean 2021 MMR (cRCT)

2014‐2017

Very low

P falciparum,

P vivax

Artemisinin resistance: Kelch 13 mutation in 57% of samples at baseline

DHAp with PQ

3 rounds administered 1 month apart over 3 months

4622

(86% in round 1, 86% in round 2, 88% in round 3)

No drug and no placebo

ITNs, routine malaria control by village health workers

  • Parasitaemia prevalence (31)

  • Adverse effects

Molineaux 1980 NGA (CBA)

1970‐1975

High

P falciparum,

P malariae,

P ovale

ND

SP

(Low frequency MDA)

9 rounds administered 10 weeks apart over 18 months

14,129

(73% to 92% per round)

No drug and no placebo

IRS

  • Parasitaemia prevalence (0)

  • Gametocytaemia prevalence (0)

(High frequency MDA)

23 rounds administered 2 weeks apart during the wet seasons and 10 weeks apart during the dry seasons over 18 months

1810

(72% to 91% per round)

Morris 2018 TZA (cRCT)

2016‐2017

Very low

P falciparum,

P malariae,

P ovale, and

P vivax

No evidence of resistance to first line treatment AS‐AQ

DHAp with PQ

2 rounds administered 4 weeks apart over 6 weeks

10,944

(91% in round 1, 88% in round 2)

No drug and no placebo

IRS and ITNs

  • Parasitaemia prevalence (0)

  • Confirmed malaria illness incidence (14)

  • Adverse effects

Pongvongsa 2018 LAO (cRCT)

2016‐2017

Low

P falciparum,

P vivax

ND

DHAp with PQ

3 rounds administered 1 month apart over 3 months

1006 (81% in round 1, 80% in round 2, and 82% in round 3)

Delayed MDA

ITNs, uninterrupted access to case management

  • Parasitaemia prevalence (10)

  • Adverse effects

Roberts 1964 KEN (CBA)

1953‐1954

Moderate

P falciparum

ND

Pyrimethamine

2 rounds administered 1 year apart over 13 months

101,000

(95% in round 1, 93% in round 2)

No drug and no placebo

None

  • Parasitaemia prevalence (7)

Shekalaghe 2011 TZA (cRCT)

2008

Very low

P falciparum

ND

SP+AS with PQ

1 round over 16 days

1110

(95%)

Placebo

ITNs, single treatment campaign for trachoma with azithromycin

  • Parasitaemia prevalence (4)

  • Confirmed malaria illness incidence (4)

  • Gametocytaemia prevalence (4)

  • Adverse effects

Tripura 2018 KHM (cRCT)

2014‐2016

Very low

P falciparum,

P vivax

Reduced susceptibility to artemisinins and ACT partner drug resistance

DHAp

3 rounds administered 1 month apart over 3 months

858 (74% in round 1, 60% in round 2, and 71% in round 3)

Delayed MDA

ITNs, uninterrupted access to case management

  • Parasitaemia prevalence (10)

  • Confirmed malaria case incidence (9)

  • Adverse effects

von Seidlein 2003 GMB (cRCT)

1999

High

P falciparum

ND

SP+AS

1 round over 1 month

12,331

(89%)

Placebo

None

  • Parasitaemia prevalence (5)

  • Parasitaemia incidence (5)

  • Gametocytaemia prevalence (5)

  • Malaria‐specific mortality

  • Adverse effects

von Seidlein 2019 VNM (cRCT)

2013‐2015

Very low

P falciparum,

P vivax

No evidence of resistance to DHAp at the start of study, but treatment failure to DHAp has increased following study

DHAp with PQ

3 rounds administered 1 month apart over 3 months

1439 (83% in round 1, 98% in round 2, and 99% in round 3)

Delayed MDA

ITNs, uninterrupted access to case management

  • Parasitaemia prevalence (10)

  • Adverse effects

ACT = artemisinin‐based combination therapy, AQ = amodiaquine, AS = artesunate, CBA = controlled before‐and‐after study, CQ = chloroquine, cRCT = cluster‐randomized controlled trial, DHAp = dihydroartemisinin piperaquine, ITNs = insecticide‐treated bed nets, IRS = indoor residual spraying, MDA = mass drug administration, PQ = primaquine, SP = sulfadoxine‐ (or sulfalene‐) pyrimethamine, NA = not applicable, ND = not described.

aMalaria endemicity classified as very low (> 0% to < 1%), low (1% to < 10%), moderate (10% to < 35%) or high (≥ 35%) (WHO 2017).
bCo‐interventions were balanced across intervention and control groups, as per inclusion criteria.
cPost‐MDA refers to the length of time, in months, after the last round of MDA that the outcome was evaluated.

Figures and Tables -
Table 1. Description of studies
Navigate to table in Review
Table 2. Description of outcomes

Study ID (design)

Parasitaemia prevalence

Parasitaemia incidence

Confirmed malaria illness incidence

All‐cause or malaria‐specific mortality

Gametocytaemia prevalence

Adverse effects

Eisele 2020 ZMBa (cRCT)

Yes

Yes

Yes

No

No

Yes

Eisele 2020 ZMBb (cRCT)

Yes

Yes

Yes

No

No

Yes

Escudie 1962 BFA (CBA)

Yes

No

No

No

Yes

No

Landier 2017 MMRa (cRCT)

Yes

No

Yes

No

No

Yes

McLean 2021 MMR (cRCT)

Yes

No

No

No

No

Yes

Molineaux 1980 NGA (CBA)

Yes

No

No

No

Yes

No

Morris 2018 TZA (cRCT)

Yes

No

Yes

No

No

Yes

Pongvongsa 2018 LAO (cRCT)

Yes

No

No

No

No

Yes

Roberts 1964 KEN (CBA)

Yes

No

No

No

No

No

Shekalaghe 2011 TZA (cRCT)

Yes

No

Yes

No

Yes

Yes

Tripura 2018 KHM (cRCT)

Yes

No

Yes

No

No

Yes

von Seidlein 2003 GMB (cRCT)

Yes

Yes

Yes

Yes

Yes

Yes

von Seidlein 2019 VNM (cRCT)

Yes

No

No

No

No

Yes

CBA = controlled before‐and‐after study, cRCT = cluster‐randomized controlled trial
Figures and Tables -
Table 2. Description of outcomes
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Table 3. Difference‐in‐differences analysis of P falciparum parasitaemia prevalence in non‐randomized studies

Study

Intervention, % (n)

Control % (n)

Difference‐in‐differences, percentage pointsa

Pre‐MDA

During MDA

Post‐MDA

Pre‐MDA

During MDA

Post‐MDA

During MDA

Post‐MDA

1 to 3 months

4 to 6 months

7 to 12 months

1 to 3 months

4 to 6 months

7 to 12 months

1 to 3 months

4 to 6 months

7 to 12 months

Escudie 1962 BFAb

Low frequency MDA with AQ‐PQ or CQ‐PQ

67.6 (190)

21.6 (75)

38.3 (105)

ND

ND

59.4 (129)

74.8 (517)

386 (72.3)

ND

ND

‐61.4

‐42.1

ND

ND

High frequency MDA with AQ‐PQ or CQ‐PQ

33.6 (131)

12.6 (59)

61.4 (286)

ND

ND

59.4 (129)

74.8 (517)

386 (72.3)

ND

ND

‐36.3

14.9

ND

ND

Molineaux 1980 NGAc

Low frequency MDA with SP

41.8 (525)

1.9 (40)

ND

ND

ND

49.1 (493)

32.5 (380)

ND

ND

ND

‐23.2

ND

ND

ND

High frequency MDA with SP

44.9 (754)

7.3 (109)

ND

ND

ND

49.1 (493)

32.5 (380)

ND

ND

ND

‐20.9

ND

ND

ND

Roberts 1964 KEN

MDA with pyrimethamine

8.3 (25)

9 (188)

2.9 (26)

(27) (4.5)

(15) (5)

18 (154)

34.4 (723)

40.7 (366)

37 (222)

26 (78)

‐15.8

‐28.1

‐22.8

‐11.3

AQ = amodiaquine, CQ = chloroquine, MDA = mass drug administration, ND = no data, PQ = primaquine, SP = sulfalene‐pyrimethamine

aCalculated as difference in proportion at the time period of during MDA or post‐MDA minus the proportion at pre‐MDA in the intervention and control separately and the difference in these two proportion differences between the intervention and control groups.
bMDA with AQ‐PQ or CQ‐PQ either every 4 weeks ('low frequency MDA') or every 2 weeks ('high frequency MDA').
cMDA with sulfalene‐pyrimethamine either every 10 weeks (low frequency MDA') or every 2 weeks during the wet season and every 10 weeks during the dry season ('high frequency MDA') to all ages except infants prior to their first malaria episode.

Figures and Tables -
Table 3. Difference‐in‐differences analysis of P falciparum parasitaemia prevalence in non‐randomized studies
Navigate to table in Review
Table 4. Difference‐in‐differences analysis of P falciparum gametocytaemia prevalence in non‐randomized studies

Study

Intervention, % (n)

Control, % (n)

Difference‐in‐differences

percentage pointa

Pre‐MDA

During MDA

Post‐MDA

1 to 3 months

Pre‐MDA

During MDA

Post‐MDA

1 to 3 months

During MDA

Post‐MDA

1 to 3 months

Escudie 1962 BFAb

Low frequency MDA with AQ‐PQ or CQ‐PQ

20.3 (57)

0.9 (3)

38.3 (35)

19.4 (42)

14 (97)

19.1 (102)

‐14.1

18.3

High frequency MDA with AQ‐PQ or CQ‐PQ

8.2 (32)

1.9 (9)

61.4 (107)

19.4 (42)

14 (97)

19.1 (102)

‐1.0

53.4

Molineaux 1980 NGAc

Low frequency MDA with SP

10.1 (127)

0.6 (12)

ND

12.4 (124)

7.9 (92)

ND

‐5.0

ND

High frequency MDA with SP

12.4 (208)

3.2 (48)

ND

12.4 (124)

7.9 (92)

ND

‐4.7

ND

AQ = amodiaquine, CQ = chloroquine, MDA = mass drug administration, ND = no data, SP = sulfalene‐pyrimethamine

aCalculated as difference in proportion at the time period of during MDA or post‐MDA minus the proportion at pre‐MDA in the intervention and control separately and the difference in these two proportion differences between the intervention and control groups.
bMDA with AQ‐PQ or CQ‐PQ either every 4 weeks ('low frequency MDA') or every 2 weeks ('high frequency MDA').
cMDA with sulfalene‐pyrimethamine either every 10 weeks ('low frequency MDA') or every 2 weeks during the wet season and every 10 weeks during the dry season ('high frequency MDA') to all ages except infants prior to their first malaria episode.

Figures and Tables -
Table 4. Difference‐in‐differences analysis of P falciparum gametocytaemia prevalence in non‐randomized studies
Navigate to table in Review
Comparison 1. MDA versus no MDA in moderate to high endemicity (cRCTs) on P falciparum outcomes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Parasitaemia prevalence (P falciparum) Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.1.1 Baseline before MDA

2

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.1.2 During MDA

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.1.3 Post‐MDA 1‐3 months

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.1.4 Post‐MDA 4‐6 months

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.2 Parasitaemia incidence (P falciparum) Show forest plot

2

Rate Ratio (IV, Fixed, 95% CI)

Totals not selected

1.2.1 Post‐MDA 1‐3 months

1

Rate Ratio (IV, Fixed, 95% CI)

Totals not selected

1.2.2 Post‐MDA 4‐6 months

1

Rate Ratio (IV, Fixed, 95% CI)

Totals not selected

1.3 Confirmed malaria illness incidence (P falciparum) Show forest plot

1

Rate Ratio (IV, Fixed, 95% CI)

Totals not selected

1.3.1 Baseline before MDA

1

Rate Ratio (IV, Fixed, 95% CI)

Totals not selected

1.3.2 Post‐MDA 1‐3 months

1

Rate Ratio (IV, Fixed, 95% CI)

Totals not selected

1.4 Gametocytaemia prevalence (P falciparum) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.4.1 Baseline before MDA

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.4.2 Post‐MDA 4‐6 months

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.5 Malaria‐specific mortality Show forest plot

1

Risk Ratio (IV, Fixed, 95% CI)

Totals not selected

1.5.1 Post‐MDA 4‐6 months

1

Risk Ratio (IV, Fixed, 95% CI)

Totals not selected
Figures and Tables -
Comparison 1. MDA versus no MDA in moderate to high endemicity (cRCTs) on P falciparum outcomes
Navigate to table in Review
Comparison 2. MDA versus no MDA in very low to low endemicity (cRCTs) on P falciparum outcomes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 Parasitaemia prevalence (P falciparum) Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1.1 Baseline before MDA

6

2093

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.62, 1.26]

2.1.2 During‐MDA

2

991

Risk Ratio (M‐H, Fixed, 95% CI)

0.26 [0.07, 0.94]

2.1.3 Post‐MDA <1 month

1

234

Risk Ratio (M‐H, Fixed, 95% CI)

0.12 [0.03, 0.52]

2.1.4 Post‐MDA 1‐3 months

7

5718

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.15, 0.41]

2.1.5 Post‐MDA 4‐6 months

4

3129

Risk Ratio (M‐H, Fixed, 95% CI)

0.63 [0.36, 1.12]

2.1.6 Post‐MDA 7‐12 months

5

3704

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.55, 1.36]

2.1.7 Post‐MDA 13‐18 months

1

243

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.20, 3.34]

2.1.8 Post‐MDA 19‐24 months

1

239

Risk Ratio (M‐H, Fixed, 95% CI)

0.34 [0.06, 1.97]

2.1.9 Post‐MDA 25‐30 months

1

242

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.22, 3.62]

2.1.10 Post‐MDA 31‐36 months

1

246

Risk Ratio (M‐H, Fixed, 95% CI)

1.25 [0.25, 6.31]

2.2 Parasitaemia incidence (P falciparum) Show forest plot

1

Rate Ratio (IV, Fixed, 95% CI)

Totals not selected

2.2.1 Post‐MDA 1‐3 months

1

Rate Ratio (IV, Fixed, 95% CI)

Totals not selected

2.3 Confirmed malaria illness incidence (P falciparum) Show forest plot

4

Rate Ratio (IV, Fixed, 95% CI)

Subtotals only

2.3.1 Baseline before MDA

3

Rate Ratio (IV, Fixed, 95% CI)

0.87 [0.45, 1.69]

2.3.2 Post‐MDA 1‐3 months

2

Rate Ratio (IV, Fixed, 95% CI)

0.58 [0.12, 2.73]

2.3.3 Post‐MDA 4‐6 months

1

Rate Ratio (IV, Fixed, 95% CI)

0.93 [0.07, 12.43]

2.3.4 Post‐MDA 7‐12 months

3

Rate Ratio (IV, Fixed, 95% CI)

0.47 [0.21, 1.03]

2.3.5 Post‐MDA 13‐18 months

1

Rate Ratio (IV, Fixed, 95% CI)

0.77 [0.20, 3.03]
Figures and Tables -
Comparison 2. MDA versus no MDA in very low to low endemicity (cRCTs) on P falciparum outcomes
Navigate to table in Review
Comparison 3. MDA versus no MDA in very low to low endemicity (cRCTs) on P vivax outcomes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

3.1 Parasitaemia prevalence (P vivax) Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1.1 Baseline before MDA

5

3187

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.86, 1.21]

3.1.2 Post‐MDA <1 month

1

234

Risk Ratio (M‐H, Fixed, 95% CI)

0.18 [0.08, 0.40]

3.1.3 Post‐MDA 1‐3 months

5

2673

Risk Ratio (M‐H, Fixed, 95% CI)

0.15 [0.10, 0.24]

3.1.4 Post‐MDA 4‐6 months

4

3299

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.63, 0.95]

3.1.5 Post‐MDA 7‐12 months

5

4406

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.94, 1.34]

3.1.6 Post‐MDA 13‐18 months

1

243

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.44, 1.48]

3.1.7 Post‐MDA 19‐24 months

1

239

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.38, 1.83]

3.1.8 Post‐MDA 25‐30 months

1

242

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.41, 1.94]

3.1.9 Post‐MDA 31‐36 months

1

246

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.44, 3.29]

3.2 Confirmed malaria illness incidence (P vivax) Show forest plot

2

Rate Ratio (IV, Fixed, 95% CI)

Subtotals only

3.2.1 Baseline before MDA

1

Rate Ratio (IV, Fixed, 95% CI)

1.74 [0.67, 4.53]

3.2.2 Post‐MDA 7‐12 months

2

Rate Ratio (IV, Fixed, 95% CI)

1.38 [0.97, 1.95]
Figures and Tables -
Comparison 3. MDA versus no MDA in very low to low endemicity (cRCTs) on P vivax outcomes
Navigate to table in Review
Comparison 4. Supplemental analysis: post‐hoc subgroup analysis by continent

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

4.1 Plasmodium falciparum parasitaemia prevalence post‐MDA 1‐3 months Show forest plot

7

5718

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.15, 0.41]

4.1.1 Africa

2

1033

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.32, 2.98]

4.1.2 Asia

5

4685

Risk Ratio (M‐H, Fixed, 95% CI)

0.19 [0.11, 0.33]
Figures and Tables -
Comparison 4. Supplemental analysis: post‐hoc subgroup analysis by continent
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