Decreased bioefficacy of long-lasting insecticidal nets and the resurgence of malaria in Papua New Guinea

Abstract

Background: Papua New Guinea (PNG) has the highest malaria transmission outside of Africa and long-lasting insecticidal nets (LLIN) are the only vector-control tool distributed country-wide. LLIN were introduced into PNG in about 2005 and have been attributed to have had a huge impact on malaria transmission, with reductions in malaria prevalence observed from 15.7% (2008) to 1% (2014). Since 2015, malaria indicators in PNG have risen significantly. Similar trends have been observed in several African nations. In the present study, we observed a drastic reduction in bioefficacy of LLIN collected both from communities (used nets) and prior to use (new nets). We hypothesise that decreased bioefficacy of LLINs is a major contributor to the observed malaria resurgence in PNG and possibly in other parts of the world. Methods: New LLIN in original and unopened packaging (n=192) with a range of manufacturing dates from 2007-2019 were collected either directly from consignments or from households in 15 PNG provinces. Used LLIN (n=40) were collected in 2 provinces, with manufacturing dates ranging from 2008-2017. LLIN were subjected to standard WHO cone bioassays using fully susceptible An. farauti mosquitoes. A subset of LLIN was re-tested using fully susceptible An. gambiae mosquitoes in order to ensure reproducibility of results. Results: Only 7% (95% CI 4-12%) of new LLIN manufactured between 2013-2019 exhibited 100% mortality. However, 84% (95%CI: 65-84%) new nets manufactured in 2012 or before exhibited 100% mortality. Only 29 % of used LLIN less than 3 years old exhibited > 80% 24h-mortality. Results obtained in tests using An. farauti corresponded well with confirmatory tests conducted using An. gambiae. Discussion: Bioefficacy of LLIN in PNG appears to have been highly variable since 2013, with few nets manufactured since 2013 meeting WHO standards. This time-frame coincides with malaria resurgence in the country. These results may have ramifications for LLIN-based malaria control that go beyond the local PNG scenario.

Nonrandom Selection and Multiple Blood Feeding of Human Hosts by Anopheles Vectors: Implications for Malaria Transmission in Papua New Guinea

“…[11][12][13] However, decreased bioefficacy of the LLINs distributed between 2013 and 2019 against pyrethroid-susceptible vectors in natural populations in PNG has been observed and is believed to be a factor causing persistent malaria transmission in PNG. 14 Decreased bioefficacy is a result of poor quality of the LLINs and not of physiological or genetic resistance to them. The phenomenon of persistent transmission in the presence of high LLIN coverage in PNG might also be caused by mosquito behaviors such as outdoor and early evening human-biting and opportunistic host selection, which enable mosquitoes to evade the indoor-deployed LLINs.…”

Effect of short-term heating on bioefficacy of deltamethrin-coated long-lasting insecticidal nets

“…Secondly, our observations imply that bioefficacy can be manipulated by applying simple procedures. Bioefficacy testing is clearly essential in LLIN quality assurance, especially as we have shown that total AI content may not always be correlated with the ability of a product to kill or knock down mosquitoes 7 . Prequalification procedures and post-market monitoring regulations for LLINs should incorporate this knowledge, ideally by implementing well-validated and standardized methods to measure the surface bioavailable proportion of AI at multiple stages of the product evaluation process, including in recipient countries 13 .…”

“…Inspired by these novel findings and the notion of heat regeneration, sometimes mentioned in documentation associated with LLIN bioefficacy testing, especially after washing 11 , we performed similar experiments with new and unwashed Permanet 2.0 ® LLINs delivered to PNG in 2019. The LLINs used in this study were the same that exhibited very low bioefficacy in WHO cone bioassays upon arrival in PNG 7 . The purpose of these experiments was to assess whether heating LLINs in a similar way as described by Yang et al for the technical grade AI would increase bioefficacy as measured in WHO standard cone bioassays 10 .…”

“…Despite this quality assurance framework, we have recently shown that PermaNet 2.0®, LLINs with severely diminished bioefficacy were distributed in Papua New Guinea (PNG) between 2013 and 2019, unnoticed by regulatory authorities 7 . Intriguingly, despite predelivery inspection reports indicating adequate total AI content, the bioefficacy of these LLINs in standardized WHO cone bioassays was low and highly variable with an average 24h mortality of just 39.4% for new nets that had never been used or washed 7 . A study from Nicaragua, published in early 2021, showed similar deficiencies for the same LLIN product, with strikingly low mortality rates for pyrethroid susceptible mosquitoes (less than 20%) just 6 months after distribution 8 .…”

Coverage, Determinants of Use and Repurposing of Long-Lasting Insecticidal Nets Two Years After a Mass Distribution in Lihir Islands, Papua New Guinea: A Cross-Sectional Study

“…Anopheles spp phenotypic resistance to pyrethroids, the insecticides commonly used in LLIN, is not yet present in PNG [10], ruling out a contribution of insecticide resistance to the changes observed in malaria epidemiology. In contrast, decreased bioefficacy of LLINs distributed between 2013 and 2019 has been described [11], as well as behavioural adaptation of local malaria vectors towards more frequent outdoor biting earlier in the evening [12,13]. Lack of use, misuse or repurposing of LLINs may as well be related to the reduced efficacy of this particular malaria control strategy.…”