What is the aim of this review?
Insecticide-treated nets (ITNs) are a core intervention for malaria control. A previous version of this Cochrane Review showed they are very effective at reducing malaria-related death and illness. Since the review was published, many areas affected by malaria have reported mosquito populations that are resistant to the insecticides used in ITNs. The aim of this review update was to evaluate the available evidence and find out whether ITNs continue to be effective at controlling the disease. Cochrane researchers collected and analysed relevant studies and assessed the overall certainty of the evidence.
What was studied in the review?
This review update summarized trials published since the previous review that evaluated the impact of ITNs on malaria-related deaths and illness, compared to both no nets and untreated nets. After searching for relevant trials up to 18 April 2018, we identified three new randomized controlled trials (studies in which participants are assigned to a treatment group using a random method). In total, we included 23 trials, enrolling more than 275,000 adults and children, to evaluate the effectiveness of ITNs for reducing the burden of malaria. The included studies provided evidence of the impact of ITNs on infection from two types of malaria parasites, Plasmodium falciparum and Plasmodium vivax.
What are the main results of the review?
Twelve trials (nine in Africa, one in Cambodia, one in Myanmar, and one in Pakistan) assessed the impact of ITNs in comparison to no nets. From these trials, we concluded that ITNs reduce the child mortality from all causes, corresponding to a saving of 5.6 lives each year for every 1000 children protected with ITNs (high-certainty evidence). ITNs also reduce the number of P falciparum cases per person per year and the proportion of people infected with P falciparum parasites (high-certainty evidence). ITNs probably reduce the number of P vivax cases per person per year and may reduce the proportion of people infected with P vivax parasites (moderate-certainty evidence).
Eleven trials (three in sub-Saharan Africa, six in Latin America, and two in Thailand) assessed the impact of ITNs in comparison to untreated nets. From these trials, we concluded that ITNs probably reduce the child mortality from all causes, corresponding to a saving of 3.5 lives each year for every 1000 children protected with ITNs (moderate-certainty evidence). ITNs also reduce the number of P falciparum cases per person per year (high-certainty evidence), and probably reduce the proportion of people infected with P falciparum parasites (moderate-certainty evidence). Whilst ITNs may also reduce the number of P vivax cases per person per year (low-certainty evidence), it is unclear if the proportion of people infected with P vivax parasites is any lower in those using an ITN than those using an untreated net (very low certainty evidence).
In interpreting these results, we considered that there are a growing number of mosquito populations that have been shown to be able to survive exposure to the insecticides used in ITNs. However, it is currently unclear how quantitatively important this is, and this seems insufficient to downgrade the existing evidence of an effect of ITNs in preventing malaria-related mortality and illness.
Key messages
ITNs, whether compared to no nets or to untreated nets, continue to be effective at reducing child mortality and malaria-related illness in affected areas.
Although there is some evidence that insecticide resistance frequency has some effects on mosquito mortality, it is unclear how quantitatively important this is. It appeared insufficient to downgrade the strong evidence of benefit on mortality and malaria illness from the trials conducted earlier
A previous version of this Cochrane Review identified that insecticide-treated nets (ITNs) are effective at reducing child mortality, parasite prevalence, and uncomplicated and severe malaria episodes. Insecticide-treated nets have since become a core intervention for malaria control and have contributed greatly to the dramatic decline in disease incidence and malaria-related deaths seen since the turn of the millennium. However, this time period has also seen a rise in resistance to pyrethroids (the insecticide used in ITNs), raising questions over whether the evidence from trials conducted before resistance became widespread can be applied to estimate the impact of ITNs on malaria transmission today.
The primary objective of this review was to assess the impact of ITNs on mortality and malaria morbidity, incorporating any evidence published since the previous update into new and existing analyses, and assessing the certainty of the resulting evidence using GRADE.
We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) published in the Cochrane Library, MEDLINE, Embase, LILACS, the World Health Organization (WHO) International Clinical Trials Registry Platform, ClinicalTrials.gov, and the ISRCTN registry for new trials published since 2004 and up to 18 April 2018.
We included individual randomized controlled trials (RCTs) and cluster RCTs comparing bed nets or curtains treated with a synthetic pyrethroid insecticide at a minimum target impregnation dose recommended by the WHO with no nets or untreated nets.
One review author assessed the identified trials for eligibility and risk of bias, and extracted data. We compared intervention and control data using risk ratios (RRs), rate ratios, and mean differences, and presented all results with their associated 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach. We drew on evidence from a meta-analysis of entomological outcomes stratified by insecticide resistance from 2014 to inform the GRADE assessments.
Our updated search identified three new trials. A total of 23 trials met the inclusion criteria, enrolling more than 275,793 adults and children. The included studies were conducted between 1987 and 2001.
ITN versus no nets
Insecticide-treated nets reduce child mortality from all causes by 17% compared to no nets (rate ratio 0.83, 95% CI 0.77 to 0.89; 5 trials, 200,833 participants, high-certainty evidence). This corresponds to a saving of 5.6 lives (95% CI 3.6 to 7.6) each year for every 1000 children protected with ITNs. Insecticide-treated nets also reduce the incidence of uncomplicated episodes of Plasmodium falciparum malaria by almost a half (rate ratio 0.55, 95% CI 0.48 to 0.64; 5 trials, 35,551 participants, high-certainty evidence) and probably reduce the incidence of uncomplicated episodes of Plasmodium vivax malaria (risk ratio (RR) 0.61, 95% CI 0.48 to 0.77; 2 trials, 10,967 participants, moderate-certainty evidence).
Insecticide-treated nets were also shown to reduce the prevalence of P falciparum malaria by 17% compared to no nets (RR 0.83, 95% CI 0.71 to 0.98; 6 trials, 18,809 participants, high-certainty evidence) but may have little or no effect on the prevalence of P vivax malaria (RR 1.00, 95% CI 0.75 to 1.34; 2 trials, 10,967 participants, low-certainty evidence). A 44% reduction in the incidence of severe malaria episodes was seen in the ITN group (rate ratio 0.56, 95% CI 0.38 to 0.82; 2 trials, 31,173 participants, high-certainty evidence), as well as an increase in mean haemoglobin (expressed as mean packed cell volume) compared to the no-net group (mean difference 1.29, 95% CI 0.42 to 2.16; 5 trials, 11,489 participants, high-certainty evidence).
ITN versus untreated nets
Insecticide-treated nets probably reduce child mortality from all causes by a third compared to untreated nets (rate ratio 0.67, 95% CI 0.36 to 1.23; 2 trials, 25,389 participants, moderate-certainty evidence). This corresponds to a saving of 3.5 lives (95% CI -2.4 to 6.8) each year for every 1000 children protected with ITNs. Insecticide-treated nets also reduce the incidence of uncomplicated P falciparum malaria episodes (rate ratio 0.58, 95% CI 0.44 to 0.78; 5 trials, 2036 participants, high-certainty evidence) and may also reduce the incidence of uncomplicated P vixax malaria episodes (rate ratio 0.73, 95% CI 0.51 to 1.05; 3 trials, 1535 participants, low-certainty evidence).
Use of an ITN probably reduces P falciparum prevalence by one-tenth in comparison to use of untreated nets (RR 0.91, 95% CI 0.78 to 1.05; 3 trials, 2,259 participants, moderate-certainty evidence). However, based on the current evidence it is unclear whether or not ITNs impact on P vivax prevalence (1 trial, 350 participants, very low certainty evidence) or mean packed cell volume (2 trials, 1,909 participants, low certainty evidence).