PBO long-lasting insecticidal nets found to be effective in reducing malaria prevalence

Bed nets have been highly effective in protecting against malaria, but recent increase in insecticide resistance means new approaches are needed

Bed nets coated with a long-lasting chemical – called piperonyl butoxide (PBO) – combined with pyrethroid insecticide reduced the prevalence of malaria in children by 44% over one year, and 33% over two years, compared to the bed nets currently used, according to a randomized controlled trial published in The Lancet. Based on this evidence, the World Health Organization (WHO) recommends increasing coverage of PBO bed nets in areas where resistance to pyrethroids is developing.

Progress in malaria control is under threat by wide-scale resistance to the pyrethroid insecticide class currently used in indoor spraying and on current bed nets. This has resulted in a need for new types of insecticide for nets and indoor spraying.

Indoor spraying of walls and ceilings kills mosquitoes that enter the home, while bed nets prevent them from reaching and biting people during the night, and the insecticide coating the nets kills the mosquitoes. Alongside effective treatment, these interventions previously reduced deaths from malaria by 62% worldwide between 2000 and 2015, however, there is a risk that these improvements could begin to reverse due to resistance.

“Our study is the first randomized control trial to report that PBO nets were more effective than standard nets against malaria infection and transmission by pyrethroid resistant mosquitoes. It also provides the strongest evidence so far of the effect of pyrethroid resistance on the use and efficacy of standard nets,” says lead author Dr Natacha Protopopoff, London School of Hygiene & Tropical Medicine, UK. “For areas where malaria is showing heightened levels of pyrethroid resistance, replacing standard nets with PBO nets will be an important way to reduce prevalence of the infection in children. The change in WHO guidance to reflect this will affect many areas of Africa where malaria is endemic, and currently standard nets are provided.”

In this study, the authors compared standard and PBO bed nets and indoor spraying of another insecticide – called pirimiphos-methyl – in 40 villages in Muleba (Tanzania). The PBO chemical is expected to last for up to two years when applied to nets, while pirimiphos-methyl indoor spraying lasts for approximately one year. The randomized trial included four groups: households either received a PBO net with no indoor spraying, a PBO net and indoor spraying, a standard net with no indoor spraying, or a standard net and indoor spraying. Previously, there was inadequate evidence to justify swapping from standard nets to PBO nets across all areas, and concerns that the PBO chemical could interact and reduce the benefits of pirimiphos-methyl indoor spraying.

Between March 2014 and December 2016, the authors compared both types of bed nets with and without indoor spraying in a group of 7184 households in the region, including 15469 children aged six months to 14 years.

Each household received one net per two people, and 45000 of each type were distributed in the study area. The nets were the same colour and shape to avoid participants noticing any difference.

The prevalence of malaria infection in children was tested at the start of the trial. The results of indoor spraying on infection prevalence in this group were checked after nine months, and the effectiveness of the nets was assessed at nine and 21 months. Before the trial began, 65% of children were infected with malaria (2499/3861 children).

Once distributed, more than three-quarters of people used the nets (77%, 15341/19852) during the first year, and this reduced to 59% (12503/21105 people) in the second year. Of the households allocated indoor spraying, 94% (827/878) of households had been sprayed.

After nine months, malaria infection was 44% lower in the group receiving PBO nets alone than in the group receiving standard nets alone (31% [275/883] children infected in the PBO net group vs 55% [515/9329] of children in the standard nets group). This effect was sustained after 21 months where there were 33% fewer infections in children using the PBO nets (46% of children [440/958] in the PBO nets group were infected with malaria vs 68% of children [710/1044] using standard nets).

In addition, at nine months, malaria prevalence in the group who received indoor spraying and standard nets (29% [252/877] children infected) was 48% lower than in the standard net group who did not receive spraying (55% [515/932] children infected) .

However, there was limited additional benefit gained from combining the PBO nets and indoor spraying. The addition of indoor spraying did not significantly improve protection over the PBO nets alone. However, the authors also note that in areas where indoor spraying with pirimiphos-methyl already occurs, substituting PBO nets for standard nets would provide no additional benefit.

Professor Mark Rowland, London School of Hygiene & Tropical Medicine, UK, who led the coordination with WHO, says:

We are pleased that the WHO has revised its policy on the basis of this trial. This will ensure insecticide treated nets now used by many millions of people in Africa and elsewhere will remain an effective intervention for malaria control, and justifies the continued investment and research on new insecticides for use on nets.

The authors note some limitations, including that the participants could not be blinded to the use of indoor spraying in their homes, which could have reduced attendance at clinic sessions due to a belief that malaria would not be an issue as a result of the spraying and nets. However, attendance was similar across all groups, so this is unlikely to have affected the results.

The indoor spraying used in this study was effective and lasted for a year, which is longer than many other insecticides. The authors will study the nets for another year to see whether they remain effective with low PBO levels.

Writing in a linked Comment, Dr Gerry Killeen, Liverpool School of Tropical Medicine, UK, and Ifakara Health Institute, Tanzania, says:

PBO long-lasting insecticidal nets are expected to be more expensive than those with a single active ingredient, and no formal cost-effectiveness estimates or comparisons are presented by Protopopoff and colleagues. Nevertheless, although indoor residual spraying with expensive alternatives to pyrethroids is recommended for insecticide resistance management and can improve malaria vector control impact, it has proven too expensive to scale-up. So, although the shift to PBO long-lasting insecticidal nets presents a challenge to low-income countries and their public sector funding partners, these products probably represent a more realistic ambition than universal coverage with indoor residual spraying using prohibitive quantities of relatively expensive alternatives to pyrethroids. Also, such a shift would set an invaluable precedent for market entry of further long-lasting insecticidal net products combining two insecticide classes that are currently awaiting WHO prequalification.

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