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The authors recently reported that long-lasting insecticidal nets (LLINs) distributed in Papua New Guinea (PNG) between 2013 and 2019, exhibited severely diminished efficacy to knock down and kill susceptible Anopheles mosquitoes. This coincided with a rise in malaria observed in PNG since 2015. Here, the authors show that LLIN bioefficacy is increased by heating LLINs prior to WHO cone bioassays. Unused LLINs with low bioefficacy, delivered to PNG in 2019, were heated to 120°C for 5 minutes. Cone bioassays were performed before and at 1 hour, 7 days, and 30 days after heating. This led to a significant increase in 24-hour mortality (17–61%) and 60-minute knock down (31–72%). The effect was sustained over 30 days. Bioassays are crucial in quality assurance of LLIN products. Our findings indicate that bioefficacy of LLINs can be increased by heating. This may have implications for quality assurance procedures used to assess LLINs.

Background Long-lasting insecticidal nets (LLINs) play a key role in reducing malaria transmission in endemic countries. In a previous study, the authors demonstrated a substantial decrease in the bioefficacy of LLINs for malaria prevention delivered to Papua New Guinea (PNG) between 2013 and 2019. This coincided with a rise in malaria cases in the country. The present study was aimed at determining the underlying cause of the reduced bioefficacy observed in these LLINs. The main hypothesis was that a change in the coating formulation of the respective LLIN product was responsible, and had led to significantly altered product properties and performance. Methods A set of PermaNet® 2.0 LLIN samples (n = 12) manufactured between 2007 and 2019 was subjected to combustion ion chromatography in order to understand the chemistry of the LLIN polymer coating formulation. In addition, World Health Organization (WHO) LLIN standard wash tests and cone bioassays were conducted to further characterize the change in product performance that occurred between 2012 and 2013. Results High polymer fluorine content (average 3.2 g/kg) was measured in PermaNet® 2.0 manufactured up to 2012, whereas nets which were manufactured after 2012 contained very little polymer fluorine (average 0.04 g/kg) indicating a coating formulation change from a fluorocarbon (FC)-based to a non-FC-based formulation. The coating formulation change as part of the manufacturing process thus resulted in a significant reduction in bioefficacy. In addition, the manufacturing change affected wash resistance leading to a faster reduction in 24 h mosquito mortality in the non-FC-coated product with consecutive washes. Conclusion A change in coating formulation of PermaNet® 2.0 resulted in reduced product performance in PNG. Post-2012 PermaNet® 2.0 LLINs should not be considered to be the same product as PermaNet® 2.0 LLINs produced prior to and in 2012. Coating formulation changes should be validated to not impact LLIN product performance.

In a study published in Nature Communications in August 2020, we demonstrated an abrupt decrease in the bioefficacy of long-lasting insecticidal nets (LLINs) for malaria prevention delivered to Papua New Guinea (PNG) between 2012 and 2013. This coincided with a rise in malaria cases in the country. At the time of publication of the original article, we were unable to pinpoint the exact reasons for the observed shift towards inferior product performance and stated that "further studies are required to determine the underlying cause of the observed reduced bioefficacy of these LLINs" 1. Due to the potentially significant public health implications (hundreds of millions of this specific LLIN product had been distributed globally), our study led to discussions and speculation among stakeholders. Here, we present data unequivocally showing that the observed reduction in the ability to kill mosquitoes of these LLINs is a direct result of a manufacturing change that occurred at the same time.

Background: Long lasting insecticidal nets (LLIN) are a key vector control tool used for the prevention of malaria. Active ingredient (AI) measurements in LLIN are essential for evaluating their quality and effectiveness. The main aim of the present study was to determine the utility of X-ray fluorescence (XRF) spectroscopy as a suitable in-field tool for total AI quantification in LLINs. Methods: New and unused LLIN samples containing deltamethrin (PermaNet 2.0, n = 35) and alpha-cypermethrin (SafeNet, n = 43) were obtained from batches delivered to PNG for mass distribution. Insecticides were extracted from the LLINs using a simple extraction technique and quantified using liquid chromatography mass spectrometry (LC-MS). The LC-MS results were correlated with in-field XRF spectroscopy measurements on the same nets. Operators were blinded towards the identity of the nets. Bioefficacy of the LLIN samples was tested using WHO cone bioassays and test results were correlated with total AI content. Results: The results indicate a close agreement between the quantitative XRF and LC-MS. Interestingly, the total AI content was negatively correlated with bioefficacy in PermaNet 2.0 (especially, in recently manufactured nets). In contrast, AI content was positively correlated with bioefficacy in SafeNet These results indicate that the chemical content analysis in predelivery inspections does not always predict bioefficacy well. Conclusion: XRF is a promising in-field method for quantification of both deltamethrin and alpha-cypermethrin coated LLINs. Since total AI content is not always a predictor of the efficacy of LLIN to kill mosquitoes, bioefficacy measurements should be included in predelivery inspections.

We recently reported that long-lasting insecticidal nets (LLINs) distributed in Papua New Guinea (PNG) between 2013 and 2019, exhibited severely diminished efficacy to knock down and kill susceptible Anopheles mosquitoes. This coincided with a rise in malaria observed in PNG since 2015. Here we show that LLIN bioefficacy is increased by heating LLINs prior to WHO cone bioassays. Unused LLINs with low bioefficacy, delivered to PNG in 2019, were heated to 120 degrees Celsius for 5 minutes. Cone bioassays were performed before and at 1 h, 7 days and 30 days after heating. This led to a significant increase in 24 h mortality (17% to 61%) and 60 min knock down (31% to 72%). The effect was sustained over 30 days. Bioassays are crucial in quality assurance of LLIN products. Our findings indicate that bioassay results can easily be manipulated. This may have implications for quality assurance procedures used to assess LLINs.