Scolaris Content Display Scolaris Content Display

Cochrane Database of Systematic Reviews

Repelentes de mosquitos para la prevención del paludismo

Information

DOI:
https://doi.org/10.1002/14651858.CD011595.pub2Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 06 February 2018see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Infectious Diseases Group

Classified:
  1. Up to date

    All studies incorporated from most recent search

    All eligible published studies found in the last search (26 Jun, 2017) were included and four ongoing studies have been identified (see 'Characteristics of ongoing studies' section)

    Assessed: 2 April 2019

Copyright:
  1. Copyright © 2018 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.

Article metrics

Altmetric:

Cited by:

Cited 0 times via Crossref Cited-by Linking

Collapse

Authors

  • Marta F Maia

    Correspondence to: Public Health and Epidemiology, Swiss Tropical and Public Health Institute, Basel, Switzerland

    [email protected]

    [email protected]

    Department of Biosciences, Kenya Medical Research Institute ‐ Wellcome Trust Programme, Kilifi, Kenya

  • Merav Kliner

    Health Protection Team, Public Health England North West, Manchester, UK

  • Marty Richardson

    Cochrane Infectious Diseases Group, Liverpool School of Tropical Medicine, Liverpool, UK

  • Christian Lengeler

    Public Health and Epidemiology, Swiss Tropical and Public Health Institute, Basel, Switzerland

  • Sarah J Moore

    Public Health and Epidemiology, Swiss Tropical and Public Health Institute, Basel, Switzerland

Contributions of authors

MM, MV, and SJM developed the protocol with statistical input from MR. MM and MV screened search outputs, selected trials for inclusion, extracted the data, assessed risk of bias, analysed the data and prepared the draft manuscript. MR provided statistical support. CL and SJM critically engaged with the manuscript and provided comments.

SJM is an investigator on two of the studies included in this review; however the author was not involved in decisions regarding inclusion, assessment of risk of bias, data extraction or interpretation of the results of this trial. MM and MK evaluated the trials and conducted all tasks in regard to these studies with no input from SJM.

All review authors have seen and approved the final manuscript.

Sources of support

Internal sources

  • Cochrane Infectious Diseases Group, UK.

  • Liverpool School of Tropical Medicine, UK.

External sources

  • University of Notre Dame, USA.

    Award number 261655. Salary of MM and SM.

  • Department of International Development (DFID), UK.

    Grant: 5242

Declarations of interest

MM, MK, MR, and CL have no conflicts of interest in any way related to the content of the review. They have no financial interests in relation to repellents for mosquito avoidance, either in the form of participations or incomes from commercial activities, patents, or from any form of sponsorship.

SJM has received salary coverage from BMGF research grant and PSI for two studies included in this review. However she did not have any role in deciding inclusion, assessment of risk of bias, data extraction, or interpretation of the results of those trials. In addition, SJM currently holds a research grant funded by the Deployed War Fighters Protection Fund evaluating permethrin‐treated clothing, which has been included in the review as an on‐going study. SJM declares no further known conflicts of interest.

Acknowledgements

We are indebted to the mentorship of Prof. Paul Garner of the Liverpool School of Tropical Medicine.

This work was partly supported through a grant from the Global Malaria Programme, World Health Organization.

MM was supported by a fellowship offered by the Effective Health Care Research Consortium, supported by Cochrane South Africa and the South African Medical Research Council, to attend a five‐day workshop in Cape Town to work on this review. This Consortium and the editorial base for the Cochrane Infectious Diseases Group is funded by UKaid from the UK government for the benefit of low‐ and middle‐income countries (Grant: 5242). The views expressed in this publication do not necessarily reflect UK government policy.

Version history

Published

Title

Stage

Authors

Version

2018 Feb 06

Mosquito repellents for malaria prevention

Review

Marta F Maia, Merav Kliner, Marty Richardson, Christian Lengeler, Sarah J Moore

https://doi.org/10.1002/14651858.CD011595.pub2

2015 Apr 01

Mosquito repellents for malaria prevention

Protocol

Marta F Maia, Merav Kliner, Marty Richardson, Christian Lengeler, Sarah J Moore

https://doi.org/10.1002/14651858.CD011595

Differences between protocol and review

With regard to P. vivax infections, we had originally described in the protocol that data onP. vivax from studies that had not cleared parasites at start would be excluded. However only two of the included studies, which both focused on spatial repellents, cleared parasites at start. If a study undertook a proper randomization, recrudescent infections would be similar between treatment arms. For this reason we decided to include data on P. vivax regardless of whether infections had been cleared at start or not.

We also decided to subgroup by use or not of LLINs as a co‐intervention rather than by endemicity level, compliance and diagnostic methods, as described in the protocol. This was done because we believe there was heterogeneity between studies that included and did not include LLINs as co‐interventions. Also, given that current malaria control programmes all incorporate LLINs, we believe policy makers are mostly interested in the combined effect of LLINs with topical repellents rather than these on their own.

Keywords

MeSH

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.

'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study.
Figures and Tables -
Figure 2

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

Forest plot of comparison: 1 Topical repellent compared to placebo or no treatment, outcome: 1.1 Clinical malaria caused by P. falciparum.
Figures and Tables -
Figure 3

Forest plot of comparison: 1 Topical repellent compared to placebo or no treatment, outcome: 1.1 Clinical malaria caused by P. falciparum.

Forest plot of comparison: 1 Topical repellent compared to placebo or no treatment, outcome: 1.2 P. falciparum parasitaemia.
Figures and Tables -
Figure 4

Forest plot of comparison: 1 Topical repellent compared to placebo or no treatment, outcome: 1.2 P. falciparum parasitaemia.

Forest plot of comparison: 1 Topical repellent compared to placebo or no treatment, outcome: 1.3 Clinical malaria caused by P. vivax.
Figures and Tables -
Figure 5

Forest plot of comparison: 1 Topical repellent compared to placebo or no treatment, outcome: 1.3 Clinical malaria caused by P. vivax.

Forest plot of comparison: 1 Topical repellent compared to placebo or no treatment, outcome: 1.4 P. vivax parasitaemia.
Figures and Tables -
Figure 6

Forest plot of comparison: 1 Topical repellent compared to placebo or no treatment, outcome: 1.4 P. vivax parasitaemia.

Forest plot of comparison: 2 ITC compared to placebo or no treatment, outcome: 2.1 Clinical malaria caused by P. falciparum.
Figures and Tables -
Figure 7

Forest plot of comparison: 2 ITC compared to placebo or no treatment, outcome: 2.1 Clinical malaria caused by P. falciparum.

Forest plot of comparison: 2 ITC compared to placebo or no treatment, outcome: 2.2 Clinical malaria caused by P. vivax.
Figures and Tables -
Figure 8

Forest plot of comparison: 2 ITC compared to placebo or no treatment, outcome: 2.2 Clinical malaria caused by P. vivax.

Forest plot of comparison: 3 Spatial repellents compared to placebo or no treatment, outcome: 3.1 Plasmodium spp. parasitaemia.
Figures and Tables -
Figure 9

Forest plot of comparison: 3 Spatial repellents compared to placebo or no treatment, outcome: 3.1 Plasmodium spp. parasitaemia.

Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 1 Clinical malaria caused by Plasmodium falciparum.
Figures and Tables -
Analysis 1.1

Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 1 Clinical malaria caused by Plasmodium falciparum.

Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 2 Plasmodium falciparum parasitaemia.
Figures and Tables -
Analysis 1.2

Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 2 Plasmodium falciparum parasitaemia.

Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 3 Clinical malaria caused by Plasmodium vivax.
Figures and Tables -
Analysis 1.3

Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 3 Clinical malaria caused by Plasmodium vivax.

Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 4 Plasmodium vivax parasitaemia.
Figures and Tables -
Analysis 1.4

Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 4 Plasmodium vivax parasitaemia.

Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 5 Anaemia.
Figures and Tables -
Analysis 1.5

Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 5 Anaemia.

Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 6 All‐cause fever.
Figures and Tables -
Analysis 1.6

Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 6 All‐cause fever.

Study

Follow up length

Method

Compliance repellent arm

Compliance treatment arm

Chen‐Hussey 2013

Monthly

Self reporting

Estimating weight of repellent bottles.

61.3%

62.2%

Hill 2007

Monthly

Self reporting

Random unanounced "sniff check"

Estimating weight of repellent bottles.

98.5%

98.5%

McGready 2001

Weekly

Self reporting

Random spot checks

Unclear

Unclear

Sangoro 2014a

Monthly

Self reporting

Mean number of bottles issued to each household

Unclear

Unclear

Sluydts 2016

Non‐periodic

Self reporting

Observational studies

Unclear

Unclear

Figures and Tables -
Analysis 1.7

Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 7 Adherence to the intervention.

Study

Follow up length

Method

Unit

Description of

adverse events

Intervention arm

Control arm

Hill 2007

Monthly surveys

Interview

Even per household

None reported

0/424

0/436

McGready 2001

Weekly surveys

Interview

Unclear

6% of the participants

reported skin warming sensation.

Unclear

Unclear

Rowland 2004

End of trial

Interviews and

questionnaires to 20 households

from each treatment arm

Event per household

Skin irritation

1/20

0/20

Sluydts 2016

Unclear

Unclear

Unclear

Not described

41/unclear

Figures and Tables -
Analysis 1.8

Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 8 Adverse events.

Comparison 2 ITC compared to placebo or no treatment, Outcome 1 Clinical malaria caused by Plasmodium falciparum.
Figures and Tables -
Analysis 2.1

Comparison 2 ITC compared to placebo or no treatment, Outcome 1 Clinical malaria caused by Plasmodium falciparum.

Comparison 2 ITC compared to placebo or no treatment, Outcome 2 Clinical malaria caused by Plasmodium vivax.
Figures and Tables -
Analysis 2.2

Comparison 2 ITC compared to placebo or no treatment, Outcome 2 Clinical malaria caused by Plasmodium vivax.

Study

Follow up length

Method

Unit

Description of adverse events

Intervention arm

Control arm

Rowland 1999

16 weeks

Interview

Event per household

None reported

0/438

0/387

Soto 1995

End of trial

Interview

Event per participant

Skin irritation

2/229

0/229

Figures and Tables -
Analysis 2.3

Comparison 2 ITC compared to placebo or no treatment, Outcome 3 Adverse events.

Comparison 3 Spatial repellents compared to placebo or no treatment, Outcome 1 Plasmodium spp. parasitaemia.
Figures and Tables -
Analysis 3.1

Comparison 3 Spatial repellents compared to placebo or no treatment, Outcome 1 Plasmodium spp. parasitaemia.

Study

Follow up length

Method

Compliance control arms

Compliance treatment arms

Hill 2014

monthly survey

Self reporting

Counting of empty coil boxes

No treatment arm: 89.3%

LLINs only arm: 97.8%

Repellent coils arm: 98.6%

Repellent coils + LLINs arm: 98.5%

Figures and Tables -
Analysis 3.2

Comparison 3 Spatial repellents compared to placebo or no treatment, Outcome 2 Adherence to the intervention.

Comparison 3 Spatial repellents compared to placebo or no treatment, Outcome 3 Reduction in mosquito bites.
Figures and Tables -
Analysis 3.3

Comparison 3 Spatial repellents compared to placebo or no treatment, Outcome 3 Reduction in mosquito bites.

Study

Follow‐up length

Method

Unit

Description of adverse events

Intervention arm

Control arm

Syafruddin 2014

6 months

Interviews

Random spot‐checks

None described

None reported

None reported

Figures and Tables -
Analysis 3.4

Comparison 3 Spatial repellents compared to placebo or no treatment, Outcome 4 Adverse events.

Summary of findings for the main comparison. Topical repellents compared to placebo or no treatment for malaria prevention

Topical repellents compared to placebo or no treatment for malaria prevention

Patient or population: malaria prevention
Setting: malaria‐endemic regions
Intervention: topical repellents
Comparison: placebo or no treatment

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with Placebo or no treatment

Risk with Topical repellents

Clinical malaria: P. falciparum

39 per 1000

25 per 1000
(15 to 41)

RR 0.65
(0.40 to 1.07)

4450
(3 studies)

⊕⊝⊝⊝
VERY LOW1,2,3

Due to risk of bias, inconsistency and imprecision

We do not know if topical repellents have an effect on malaria cases caused by P. falciparum. We have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect.

Parasitaemia: P. falciparum

15 per 1000

12 per 1000
(9 to 17)

RR 0.84
(0.64 to 1.12)

13,310
(4 studies)

⊕⊕⊝⊝
LOW4,5

Due to risk of bias and imprecision

Topical repellents may or may not have a protective effect against P. falciparum parasitaemia. Our confidence in the effect estimate is limited. The true effect may be substantially different from the estimation of the effect.

Clinical malaria: P. vivax

36 per 1000

48 per 1000
(36 to 64)

RR 1.32
(0.99 to 1.76)

3996
(2 studies)

⊕⊕⊝⊝
LOW6,7

Due to risk of bias and imprecision

Topical repellents may increase the number of clinical cases caused by P. vivax. Our confidence in the effect estimate is limited. The true effect may be substantially different from the estimation of the effect.

Parasitaemia: P. vivax

18 per 1000

19 per 1000
(14 to 25)

RR 1.07
(0.80 to 1.41)

9434
(3 studies)

⊕⊕⊝⊝
LOW7,8

Due to risk of bias and imprecision

Topical repellents may or may not have a protective effect against P. vivax parasitaemia Our confidence in the effect estimation is limited. The true effect may be substantially different from the estimation of the effect.

*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
Abbreviations: CI: confidence interval; RR: risk ratio; OR: odds 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.

1Downgraded by 1 for risk of bias: Sangoro 2014a used alternate allocation and reported a baseline imbalance; random sequence generation and allocation concealment were not described by Rowland 2004; and Sluydts 2016 did not have a placebo so the intervention was not blinded.
2Downgraded by 1 because of the large heterogeneity between the 3 trials. The I² statistic, which quantifies the proportion of the variation in the point estimates due to among‐study differences, was considered substantial at 50%. The subgroup analysis to some extent explained the heterogeneity but we do not believe that there is enough evidence to suggest there is a true subgroup effect given that there is no heterogeneity in the outcome parasitaemia caused by P. falciparum where studies with and without LLINs were also analysed.
3Downgraded by 1 for imprecision because the sample size is too small, the CIs are wide, the pooled effect (0.40 to 1.07) overlaps a risk ratio (RR) of 1.0 (no effect) and presents an estimate of effect ranging between beneficial and harmful.
4Downgraded by 1 for risk of bias: Hill 2007 used alternate allocation and reported a baseline imbalance; random sequence generation and allocation concealment were not described by McGready 2001.
5Downgraded by 1 for imprecision because the sample size is too small, the CIs are very wide, the pooled effect (0.62 to 1.12) overlaps a risk ratio (RR) of 1.0 (no effect) and presents an estimate of effect ranging between beneficial and harmful.
6Downgraded by 1 for risk of bias: random sequence generation and allocation concealment were not described by Rowland 2004; Sluydts 2016 was not placebo‐controlled and intervention was not blinded.
7Downgraded by 1 for imprecision because the CIs are very wide, the pooled effect (0.80 to 1.41) overlaps a risk ratio (RR) of 1.0 (no effect) and presents an estimate of effect ranging between beneficial and harmful.
8Downgraded by 1 for risk of bias: random sequence generation and allocation concealment were not described by McGready 2001.

Figures and Tables -
Summary of findings for the main comparison. Topical repellents compared to placebo or no treatment for malaria prevention
Summary of findings 2. ITC compared to placebo or no treatment for malaria prevention

ITC compared to placebo or no treatment for malaria prevention

Patient or population: malaria prevention
Setting: malaria‐endemic regions
Intervention: ITC
Comparison: placebo or no treatment

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with placebo or no treatment

Risk with ITC

Clinical malaria: P. falciparum

35 per 1000

17 per 1000
(10 to 29)

RR 0.49
(0.29 to 0.83)

997
(2 studies)

⊕⊕⊝⊝
LOW1,2

Due to risk of bias and imprecision

Insecticide‐treating clothing may have a protective effect against malaria caused by P. falciparum. Our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect.

Clinical malaria: P. vivax

116 per 1000

74 per 1000
(47 to 117)

RR 0.64
(0.40 to 1.01)

997
(2 studies)

⊕⊕⊝⊝
LOW1,2

Due to risk of bias and imprecision

Insecticide‐treated clothing may have a protective effect against malaria caused by P. vivax. Our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect.

*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
Abbreviations: CI: confidence interval; RR: risk ratio; OR: odds 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

1Downgraded by 1 for risk of bias: Soto 1995 did not describe how randomization and allocation concealment was assured; and had unclear risk of baseline bias because did not report how long soldiers in each arm were deployed to malaria endemic areas. Rowland 1999 did not describe the method used for allocation concealment.
2Downgraded by 1 for imprecision: the sample sizes and number of events are very small.

Figures and Tables -
Summary of findings 2. ITC compared to placebo or no treatment for malaria prevention
Summary of findings 3. Spatial repellents compared to placebo or no treatment for malaria prevention

Spatial repellents compared to placebo or no treatment for malaria prevention

Patient or population: malaria prevention
Setting: malaria‐endemic regions
Intervention: spatial repellents
Comparison: placebo or no treatment

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with placebo or no treatment

Risk with Spatial repellents

Parasitaemia Plasmodium spp.

10 per 1000

2 per 1000

(0 to 18)

RR 0.24

(0.03 to 1.72)

6683

(2 studies)

⊕⊝⊝⊝
VERY LOW1,2,3

Due to risk of bias, imprecision and inconsistency

We do not know if spatial repellents protect against malaria. We have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect.

*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
Abbreviations: CI: confidence interval; RR: risk ratio; OR: odds 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

1Downgraded by 1 for risk of bias: Hill 2014 was not blinded.
2Downgraded by 1 for imprecision: Hill 2014 was underpowered and reported very few events (1/3349 in the intervention and 11/3270 in the control), and the CIs ranged from no effect to large benefits. Both studies were underpowered.
3Downgraded by 1 for inconsistency: there is considerable unexplained heterogeneity between trials (I² statistic = 46%)

Figures and Tables -
Summary of findings 3. Spatial repellents compared to placebo or no treatment for malaria prevention
Table 1. Assessment of compliance

Study

Intervention group

Design

Method of assessing compliance

Unit

Follow‐up time

Compliance level1

Intervention arm

Placebo arm

Chen‐Hussey 2013

Topical repellent

cRCT

Self‐reported compliance.

Self‐reported combined with an estimation of the proportion of lotion used by the participant by weighing the returned bottles.

Percentage of self‐reported participants/night that adhered to the assigned treatment in a given month.

Participants who reported to have used the repellent and confirmed by the weight of returned bottles.

Monthly surveys

Moderate: 61.3%

Moderate: 62.2%

Hill 2007

Topical repellent

cRCT

Self‐reported compliance through questionnaires combined with an estimation of the amount used by weighing the returned bottles, and verified by unannounced “sniff checks”.

Cumulative percentage of compliant households per month.

A household was considered non‐compliant if they had reported to have not used the repellent 3 or more nights in a month or had more than 30 ml left in the bottle.

Monthly surveys

High: 98.5% (119/8164)

High: 98.5% (110/7876)

Hill 2014

Spatial repellent

cRCT

Daily recordings of compliance per household were reported by village leaders. Compliance was further confirmed by counting the number of empty mosquito coil boxes in each house.

Cumulative percentage of compliant households per month.

A household was considered non‐compliant if it did not use the coils for 3 days or longer in one month.

Monthly surveys

High

No treatment arm: 89.3%

LLIN arm: 97.8%

High

Repellent coils arm: 98.6%

Repellent coils + LLINs: 98.5%

McGready 2001

Topical repellent

RCT

Weekly self‐reporting and random spot checks.

Cumulative percentage of compliant participants per week.

Weekly surveys

Unclear

Compliance was reported to be similar across treatment arms (P = 0.24) but was not reported for each arm.

Self‐reported compliance: 90.5% (87,715/96,955)

Compliance measured by spot checks: 84.6% (1918/2267)

Sangoro 2014a

Topical repellent

cRCT

Self‐reported compliance through questionnaires combined with an estimation of the amount used by counting the empty returned bottles.

Mean number of bottles of repellent issued to each household per month.

Monthly surveys

Unclear

Authors stated that self‐reported data was unreliable so they used the data from the empty bottles to estimate compliance. Compliance was poorly reported. The authors reported mean number of bottles issued per household per month rather than estimating the compliance level for each treatment arm:

Repellent arm: 6.73 bottles (95% CI 6.51 to 6.95)

Placebo arm: 6.92 bottles (95% CI 6.68 to 7.16)

Sluydts 2016

Topical repellent

cRCT

Self‐reported compliance was assessed using questionnaires during 3 surveys in October 2012, March 2013 and October 2013.

The repellent consumption rate was measured per family every 2 weeks during the repellent distribution by visual inspection of the leftover repellent divided into categories (for example, empty, half full, full).

A social science study was done to assess the acceptability and use of repellents in 10 selected clusters.

Unit of measurement was not clearly defined.

Self‐reported compliance is likely the percentage of compliant households during the survey period but was not defined in the article.

The repellent consumption rate was not reported.

Social study reported percentage of participants observed to comply with the application of the repellent from a small selection of 10 clusters in the intervention group.

Non‐periodic surveys (in October 2012, March 2013 and October 2013) along the duration of the trial.

Self‐reported compliance was reported around 70%.

However, observational studies reported compliance between 6% and 15% .

No placebo

1Levels of compliance: high: > 80%; moderate: 50% to 79%; low: < 50%.

Figures and Tables -
Table 1. Assessment of compliance
Table 2. Epidemiology of malaria and major vector of the study region

Study

Intervention

Design

Transmission intensity1,2

Region

Main malaria vectors

Biting times

Efficacy of the intervention at repelling Anophelines tested at baseline? (V/N)

Chen‐Hussey 2013

Topical repellent

cRCT

Hypoendemic

0.83% P. falciparum

0.4% P. vivax

Measured through active case detection

South East Asia ‐ Laos

Anopheles dirus

An. minimus

An. maculatus

From 18:00 to 2:00 with peak biting time from 21.00 to 02.00.

No

Hill 2007

Topical repellent

cRCT

Hypoendemic

0.31% P. falciparum

Measured through active case detection

South America: Bolivian Amazon Region

An. darlingi

Peak biting activity between 8 p.m. and 10 p.m.

Yes

Moore 2002

Hill 2014

Spatial repellent

cRCT

Hypoendemic

0.06% P. falciparum

0.28% P. vivax

Measured through active case detection

South East Asia: Yunnan Province of China

An. sinensis

An. minimus

An. kochi

An. splendidus

An barbirostris

An. vagus

An. jeyporiensis

An. annularis

An. philippinsis

An. tessallatus

An. maculatus

An. barbumbrosus

An. dirus

An culicifacies

Given the diversity of vectors in the area the biting activity occurs from early evening extending to later in the night.

Yes

McGready 2001

Topical repellent

RCT

Mesoendemic

11.4% P. falciparum

11.8% P. vivax

Measured through active case detection

South East Asia: Thailand

Not reported

Not reported

No

Rowland 1999

Insecticide treated clothing

cRCT

Holoendemic

20.7% P. falciparum

17.6% P. vivax

Measured through passive case detection

North Western Pakistan

An. nigerrimus

An. subpictus

An. stephensi

Not reported

Yes

Rowland 2004

Topical repellent

cRCT

Mesoendemic

8.9% P. falciparum

11.7% P. vivax

Measured through passive case detection

Asia: Pakistan

An. culicifacies

An. stephensi

An. nigerrimus

An. pulcherrimus

Mosquito biting starts after dusk, peaks around 9 p.m. to 11 p.m. then declines gradually through the night.

Yes

Sangoro 2014a

Topical repellent

cRCT

Mesoendemic

6.22% P. falciparum

Measured through passive case detection

East Africa: Tanzania

An gambiae s.s.

An arabiensis

Biting activity starts early evening and continues into the later hours of the night.

Yes

Sangoro 2014c

Sluydts 2016

Topical repellent

cRCT

Hypoendemic

1.33% P. falciparum

1.85% P. vivax

Measured through active case detection

Southeast Asia: Cambodia

An. dirus s.s.

An. maculatus

An barbirostris

An. minimus s.s.

An. sawadwongporni

An aconitus

Early evening biting was common.

Yes

Van Roey 2014

Soto 1995

Insecticide‐treated clothing

RCT

Mesoendemic for P.vivax and Hypoenemic for P. falciparum

3.4% P. falciparum

10.4% P. vivax

Measured through passive case detection

South America: Colombia

Unclear

Not reported

No

Syafruddin 2014

Spatial repellent

cRCT

Holoendemic for Plasmodium spp.

70.1% Plasmodium spp.

Measured through passive case detection

Asia:

Indonesia

An. sundaicus

An. subpictus s.l.

An. indefinitus

An. vagus

An. barbirostris

An. annularis

An. maculatus

An. aconitus

An. kochi

An. tessellatus

Early evening biting was common with peaks between 18:00 and 20:00 continuing throughout the night. The high diversity of vectors also reflected diverse biting patterns.

Yes

Barbara 2011

1Transmission intensity: holo‐endemic: malaria prevalence > 15%; meso‐endemic: malaria prevalence 5% to 15%; and hypo‐endemic: malaria prevalence < 5%.
2Calculated from prevalence in the control group.

Figures and Tables -
Table 2. Epidemiology of malaria and major vector of the study region
Table 3. Malaria diagnostic methods

Study

Intervention

Design

Diagnostic method

Validated

Plasmodium species in the region

Participants screened and cleared for vivax (Y/N)

Chen‐Hussey 2013

Topical repellent

cRCT

mRDT

Yes, by PCR

80% P. falciparum

20% P. vivax

No

Hill 2007

Topical repellent

cRCT

mRDT

No

P. falciparum

P. vivax

No1

Hill 2014

Spatial repellent

cRCT

mRDTs

Yes, positive RDTs were validated through thick blood slide.

32% P. falciparum

58% P. vivax

Yes

McGready 2001

Topical repellent

RCT

Blood smear

No

P. falciparum

P. vivax

No

Rowland 1999

Insecticide‐treated clothing

cRCT

Blood smear

No

P. falciparum

P. vivax

No

Rowland 2004

Topical repellent

cRCT

Blood smear

No

P. falciparum

P. vivax

No

Sangoro 2014a

Topical repellent

cRCT

mRDT

Unclear if microscopy was used for validation of positive mRDTs

Mainly P. falciparum

No1

Sluydts 2016

Topical repellent

cRCT

PCR

No

P. falciparum

P. vivax

No

Soto 1995

Insecticide‐treated clothing

RCT

Blood smear

No

P. falciparum

P. vivax

No

Syafruddin 2014

Spatial repellent

cRCT

Blood smear

No

P. falciparum

P. vivax

Yes

1mRDT was only specific for P. falciparum.

Figures and Tables -
Table 3. Malaria diagnostic methods
Comparison 1. Topical repellent compared to placebo or no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clinical malaria caused by Plasmodium falciparum Show forest plot

3

4447

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.40, 1.07]

1.1 Without LLINs

1

869

Risk Ratio (M‐H, Random, 95% CI)

0.40 [0.23, 0.71]

1.2 With LLINS

2

3578

Risk Ratio (M‐H, Random, 95% CI)

0.84 [0.55, 1.27]

2 Plasmodium falciparum parasitaemia Show forest plot

4

13310

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.64, 1.12]

2.1 Without LLINs

1

897

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.53, 1.16]

2.2 With LLINs

3

12413

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.60, 1.38]

3 Clinical malaria caused by Plasmodium vivax Show forest plot

2

3996

Risk Ratio (M‐H, Fixed, 95% CI)

1.32 [0.99, 1.76]

3.1 Without LLINs

1

869

Risk Ratio (M‐H, Fixed, 95% CI)

1.42 [1.02, 1.99]

3.2 With LLINs

1

3127

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.64, 1.94]

4 Plasmodium vivax parasitaemia Show forest plot

3

9589

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.81, 1.43]

4.1 Without LLINs

1

897

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.68, 1.40]

4.2 With LLINs

2

8692

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.78, 1.97]

5 Anaemia Show forest plot

1

587

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.91, 1.23]

6 All‐cause fever Show forest plot

1

3496

Risk Ratio (M‐H, Fixed, 95% CI)

0.44 [0.35, 0.55]

7 Adherence to the intervention Show forest plot

Other data

No numeric data

8 Adverse events Show forest plot

Other data

No numeric data

Figures and Tables -
Comparison 1. Topical repellent compared to placebo or no treatment
Comparison 2. ITC compared to placebo or no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clinical malaria caused by Plasmodium falciparum Show forest plot

2

Risk Ratio (Fixed, 95% CI)

0.49 [0.29, 0.83]

2 Clinical malaria caused by Plasmodium vivax Show forest plot

2

Risk Ratio (Fixed, 95% CI)

0.64 [0.40, 1.01]

3 Adverse events Show forest plot

Other data

No numeric data

Figures and Tables -
Comparison 2. ITC compared to placebo or no treatment
Comparison 3. Spatial repellents compared to placebo or no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Plasmodium spp. parasitaemia Show forest plot

2

Risk Ratio (Random, 95% CI)

0.24 [0.03, 1.72]

2 Adherence to the intervention Show forest plot

Other data

No numeric data

3 Reduction in mosquito bites Show forest plot

1

16

Mean Difference (IV, Fixed, 95% CI)

‐10.8 [‐16.23, ‐5.37]

4 Adverse events Show forest plot

Other data

No numeric data

Figures and Tables -
Comparison 3. Spatial repellents compared to placebo or no treatment