The chlorfenapyr net: big win, expiry date

Three years after distribution in Misungwi, Tanzania, 22.8% of people tested in areas with chlorfenapyr-pyrethroid nets had malaria infection, compared with 37.4% in areas with standard pyrethroid-only nets (odds ratio 0.57) ¹. Most other new net types had lost their advantage by then. Chlorfenapyr nets, which pair a standard insecticide with one that works in a different way, are now the leading tool against insecticide-resistant mosquitoes. In 2024, pyrethroid-PBO and dual-active-ingredient nets made up 84% of the 168 million nets shipped to sub-Saharan Africa, up from 10% in 2019 ⁶.

The newest evidence shows both their strength and their limits. The strength: fewer infections, protection for neighbours who do not use a net, and a 30% fall in cases in a Ghanaian regional campaign. The limits: benefit fades by year three, nets wear out quickly, and mosquitoes may adapt.

The burden

The World Health Organization (WHO) estimates 282 million malaria cases and 610,000 malaria deaths in 2024 ⁶. The WHO African Region carried 94% of cases and 95% of deaths, and 75% of deaths in the region were in children under 5 years ⁶. WHO's fact sheet gives the African toll as 579,000 deaths ⁷. That is roughly 434,000 young children.

Within the WHO African Region, Nigeria accounted for 31.9% of malaria deaths, the Democratic Republic of the Congo for 11.7% and Niger for 6.1% ⁷. Tanzania, Ghana, Uganda, Mali and Burkina Faso are among the 11 African countries that together carry about two thirds of global cases and deaths ⁶.

Nets are the backbone of malaria prevention. WHO credits widespread use of insecticide-treated nets with a 70% reduction in malaria cases in Africa between 2000 and 2015 ⁶. More than 3 billion nets have been distributed ⁶. But progress has stalled. Deaths rose from 578,000 in 2015 to 610,000 in 2024, largely because populations grew, even as the mortality rate fell slightly ⁶.

One reason is insecticide resistance. Most nets since 2000 were treated with a single class of insecticide, the pyrethroids ⁶. Pyrethroid resistance has been confirmed in 48 of 53 countries that reported on it between 2020 and 2024 ⁶. A Benin study team counts insecticide resistance in malaria mosquitoes in 84 endemic countries and territories ⁵.

Use has also plateaued. In 2024, 47% of people at risk in sub-Saharan Africa slept under a net, similar to levels since 2015, and 53% of young children and pregnant women did ⁶.

How it works

A standard net does two jobs. It is a physical barrier between a sleeping child and a mosquito. And its insecticide kills or repels mosquitoes that land on it. When mosquitoes become resistant, they can land on a pyrethroid net, survive, and try again later, or bite someone else.

Dual-active-ingredient nets add a second chemical with a different action:

• Chlorfenapyr is a "pro-insecticide". It needs to be activated inside the mosquito. The Benin entomology team notes that some enzymes linked to resistance are "involved in pro-insecticide activation" ⁵. That means some resistance machinery may help chlorfenapyr work rather than block it.
• Pyriproxyfen is an insect growth regulator. It aims to reduce the fertility of mosquitoes that survive contact ⁵.
• Piperonyl butoxide (PBO) is a synergist added to boost the pyrethroid, not a second insecticide.

Because chlorfenapyr nets kill mosquitoes, not only block them, they reduce mosquito numbers for the whole community. That is why children who do not sleep under a net can still benefit ².

In an experimental-hut trial in Uganda, Oruni and colleagues found the chlorfenapyr net Interceptor G2 killed 70.6% of highly resistant Anopheles funestus and 63.2% of An. gambiae, while a pyrethroid-only net killed about 25% ¹⁰. The odds of mosquito death were 18.7 times higher (95% CI 8.05–48.6) ¹⁰. Known pyrethroid-resistance markers predicted survival against pyrethroid nets but not against the chlorfenapyr net ¹⁰.

For health workers, the practical message is unchanged: a net protects only if it is present, intact and slept under every night.

What the evidence shows

2018: the earlier case for overcoming pyrethroid resistance

Before chlorfenapyr's large trials, a 48-cluster factorial trial in Muleba, Tanzania, tested PBO nets and indoor residual spraying. Published in 2018, it found lower malaria prevalence with PBO nets than standard nets at 21 months (45% versus 62%; odds ratio 0.40, 95% CI 0.20–0.81). Adding the tested indoor spray to PBO nets brought no further benefit ¹⁴. The outcome was infection prevalence, not child mortality.

That result explains why a new net should be judged against an effective alternative as well as a pyrethroid-only net. It also cautions against generalising the later Misungwi trial's non-significant PBO result to every setting or product. Chlorfenapyr's own early trials, published in 2022 and 2023, are now part of this review, alongside their third-year follow-up.

Tanzania: benefit lasts into year three

Who and where. The National Institute for Medical Research (NIMR) in Tanzania and the London School of Hygiene & Tropical Medicine (LSHTM), with Mosha and colleagues, ran a four-arm cluster-randomised trial in Misungwi district ¹¹¹. It is registered as NCT03554616 ¹.

Design. 84 clusters were randomised 1:1:1:1 to pyrethroid-only nets (reference), chlorfenapyr-pyrethroid, pyriproxyfen-pyrethroid or PBO-pyrethroid nets ¹. All households received one net for every two people ¹. Participants and field staff were masked to allocation ¹.

Years one and two. The first two years were published in 2022 and fall within this review. 39,307 households were included and 147,230 nets were distributed in January 2019 ¹¹. At 24 months, infection prevalence in children was 45.8% with pyrethroid-only nets and 25.6% with chlorfenapyr nets (adjusted OR 0.45, 95% CI 0.30–0.67) ¹¹. Pyriproxyfen (0.79) and PBO (0.99) nets were not significantly different ¹¹.

Year-three outcome. At 36 months, infection prevalence was 37.4% (407 of 1,088) with pyrethroid-only nets and 22.8% (261 of 1,145) with chlorfenapyr nets (OR 0.57, 0.38–0.86; p=0.0069) ¹. PBO nets had an OR of 0.95 (0.64–1.42) and pyriproxyfen nets 0.82 (0.55–1.23), neither significant ¹. No side-effects were reported ¹.

Caveats. Only 22.3% of people were still using study nets at 36 months ¹. The year-3 outcome was secondary; the primary endpoint was at 24 months ¹.

Tanzania: protection for non-users

Who. Lukole and colleagues analysed the same trial ².

Design and size. Five cross-sectional surveys between 2020 and 2022 tested 22,479 children from 12,654 households with rapid diagnostic tests ².

Outcome. Where community use of dual-AI nets was above 40%, children who did not use a net were protected. Compared with non-users in pyrethroid-only clusters with over 40% use, the odds ratios were 0.44 (0.27–0.71) for chlorfenapyr, 0.55 (0.33–0.94) for PBO and 0.61 (0.37–0.99) for pyriproxyfen ². Even where chlorfenapyr net use was 40% or less, non-users showed a sign of protection (OR 0.65, 0.42–1.01), though this was just short of significance ².

Caveat. Net users were still much better protected than non-users ². Community benefit adds to personal protection; it does not replace it.

Benin: strong years one and two

Who and where. The Centre de Recherche Entomologique de Cotonou (CREC) and LSHTM, with Accrombessi and colleagues, ran a three-arm trial in Zou Department, Benin ¹². It is registered as NCT03931473 and was funded by Unitaid and the Global Fund ¹². This 2023 result is part of the expanded review.

Design and results. 60 clusters were randomised to pyriproxyfen-pyrethroid, chlorfenapyr-pyrethroid or pyrethroid-only nets, and 115,323 nets were distributed in March 2020 ¹². Over two years, malaria incidence in children was 1.03 cases per child-year with pyrethroid-only nets and 0.56 with chlorfenapyr nets (HR 0.54, 0.42–0.70) ¹². Pyriproxyfen nets were not significantly better (HR 0.86) ¹².

Benin: year three

Design and size. A secondary analysis followed a new cohort of 600 children per arm, enrolled in April 2022, through the third year after distribution ⁴.

Outcome. Incidence was 1.19 cases per child-year with pyrethroid-only nets, 0.96 with chlorfenapyr nets (HR 0.80, 0.56–1.17; p=0.25) and 1.21 with pyriproxyfen nets (HR 1.02, 0.71–1.44) ⁴. Neither difference was significant ⁴.

Why. The authors link the loss of benefit to lower net use and declining concentration of the partner insecticides in the nets ⁴. At 36 months, study-net use was 39.4% in the pyriproxyfen arm, 52.2% in the chlorfenapyr arm and 57.6% in the pyrethroid-only arm ⁴.

Ghana: a regional campaign

Who and where. Oppong and colleagues evaluated distribution of Interceptor G2 (IG2) nets in 2021 in Ghana's Western North Region ³.

Design. A Bayesian interrupted time series of monthly confirmed malaria cases reported by health facilities from 2018 to 2023, adjusted for climate ³.

Outcome. Cases fell by 30% (OR 0.696, CrI 0.623–0.778) immediately after distribution ³. The effect held at 6 months (26% reduction) and at 30 months (40%, OR 0.594, CrI 0.492–0.718) ³. Seven of the region's nine districts saw strong reductions ³.

Caveat. This is routine data without a randomised comparison group. It shows the trial benefit carrying over to a national programme, but it is weaker evidence than a trial.

Results at a glance

LimitsWhat didn't work (or the limits)

Benefit faded by year three in Benin. The chlorfenapyr net's hazard ratio moved from 0.54 over years one and two ¹² to 0.80, not significant, in year three ⁴. The benefit fades as nets wear out, use drops and the partner insecticide declines ⁴.

Other dual-AI nets did not last. In Tanzania, PBO and pyriproxyfen nets were not significantly better than standard nets at 24 or 36 months ¹¹¹. In Benin, pyriproxyfen nets gave no benefit in any year ⁴¹².

Nets do not survive three years. A 2022 study of PBO and standard nets in the same area of Tanzania found fewer than 17% of distributed nets remained in households after three years ⁹. Median functional survival was 1.6 years for PBO nets and 1.9 years for standard nets ⁹. After three years, nets had lost 55% of their pyrethroid content, and PBO nets had lost 97% of their PBO ⁹. Even so, PBO nets stayed more protective than standard nets as they aged ⁹. Plans that assume a three-year life are optimistic.

Low use limits every net. Study-net use in Tanzania fell from 72.1% at 3 months to 40.9% at 24 months ¹¹ and 22.3% at 36 months ¹.

Mosquitoes may adapt. Sovi and colleagues, with the Benin trial team, tested 19,292 mosquitoes over 36 months ⁵. Pyrethroid resistance roughly halved in the first 12 months in all arms, then rose past baseline over the next two years ⁵. After 24 months, chlorfenapyr-pyrethroid nets no longer mitigated pyrethroid-resistance selection ⁵. There was only a minimal reduction in susceptibility to chlorfenapyr itself ⁵. The authors say this "raises issues for current net-procurement schedules, which are based on an operational net lifespan of 3 years" ⁵.

Hut results vary by mosquito species. In Uganda, PBO nets blocked blood-feeding better than the chlorfenapyr net, and PBO and pyriproxyfen nets killed far fewer An. funestus ¹⁰. The best net depends on which mosquitoes dominate locally ¹⁰.

Cost and scale

Cost per DALY. In the Tanzania trial's economic analysis, chlorfenapyr nets were the most cost-effective. Compared with pyrethroid-only nets, they cost only US$19 (95% uncertainty interval 1–105) more to public providers, or $28 (11–120) more to donors, per DALY averted over two years ¹¹. They saved costs from household and societal perspectives ¹¹. The authors put plausible cost-effectiveness thresholds at $292–393 per DALY averted ¹¹.

Real-world costs. A 2026 preprint, not yet peer reviewed, by Yukich and colleagues pooled pilot evaluations in five countries ¹³. Chlorfenapyr-pyrethroid nets had the best performance, with an incidence rate ratio of 0.62 against standard nets ¹³. In one setting, the added cost was US$1.51 per case averted for chlorfenapyr nets against $18.59 for adding indoor residual spraying ¹³. The authors recommend switching from standard nets in most African settings, with chlorfenapyr nets broadly favoured ¹³. The economic results cited here are per case or per DALY averted; we do not convert them into a cost per death averted.

Scale. More than 3 billion nets have been distributed ⁶. In 2024, 84% of the 168 million nets shipped to sub-Saharan Africa were PBO or dual-active-ingredient nets ⁶.

Who funds and delivers. The Benin trials were funded by Unitaid and the Global Fund ⁴¹². National malaria programmes run the mass campaigns; Ghana's IG2 distribution in the Western North Region is one example ³. In 2024, total malaria funding was US$3.9 billion against a need of US$9.3 billion, and official development assistance fell by 21% from 2024 to 2025 ⁶. WHO reports that partner support kept net campaigns largely on track despite the cuts ⁶.

What to watch

Côte d'Ivoire: top-ups versus replacement. LSHTM is running the Net Transition Initiative trial in Tiebissou department, near Bouaké in central Côte d'Ivoire (NCT05796193) ⁸. It compares chlorfenapyr (Interceptor G2) and PBO (Veeralin) nets with standard nets, and adds arms with school-based net top-ups in years two and three ⁸. The primary outcome is malaria case incidence in children aged 6 months to 10 years, with about 1,650 participants and primary completion listed for March 2027 ⁸. It is the most direct test yet of whether topping up nets can offset the year-three fade.

Chlorfenapyr resistance. The Benin team saw only minimal change in chlorfenapyr susceptibility ⁵, but identified metabolic genes (CYP6P3 and CYP9K1) linked to resistance selection in the chlorfenapyr arm ⁵. Continued monitoring will show whether this changes.

Which net for which mosquito. The Uganda hut trial suggests PBO and pyriproxyfen nets may suit areas dominated by An. gambiae, and chlorfenapyr nets areas with highly resistant An. funestus ¹⁰. National programmes will need local vector maps to decide.

Replacement cycles. The strongest open question is whether funders will pay for replacement every two years instead of three. The Benin resistance data ⁵, the Benin year-3 result ⁴ and net-survival data ⁹ all point in that direction.

What it means

For ministries of health and national malaria programmes. Chlorfenapyr nets are a large gain for children in areas where mosquitoes resist pyrethroids. They outperformed standard nets in Tanzania for three years ¹, protected children who did not use them ² and cut cases by 30% in Ghana's Western North Region ³. Prioritise them where pyrethroid resistance is high, budget for shorter replacement cycles, and fund entomological monitoring so that any loss of chlorfenapyr susceptibility is detected early ⁵.

For funders. The extra cost per DALY is small ¹¹. But the Benin year-3 result ⁴ and the resistance data ⁵ point to an expiry date. Buying a better net and then leaving it in place for three years wastes part of the gain. Paying for replacement at about two years, or for top-ups, protects the investment. Keeping community use above 40% also protects non-users ².

For researchers. The field needs peer-reviewed cost per death averted, results from top-up strategies ⁸, and new active ingredients for rotation.

For health workers. The message to families is simple: use the net every night, including for the youngest children, and replace it when it is torn or lost. A new net does more than an old one.