Dr Itoh of Sumitomo Chemical Company criticizes our evaluations of long-lasting insecticide-treated nets (LLINs) on two main grounds: (1) our results are inconsistent with the existing literature and (2) the test we used – the WHO cone test – is inappropriate for testing the Olyset® net. To date, we are aware of only nine studies on Olyset® published in peer-reviewed literature, and the majority of these were short-term, laboratory-based or experimental hut trials. There have been only three published field studies measuring either malaria transmission or morbidity outcomes; none has yet evaluated the effect of Olyset® on all-cause or malaria-specific child mortality. One of these studies did demonstrate a reduction in malaria transmission (Faye et al. 1998) while a second showed a reduction in malaria attacks (Henry et al. 1999) but the third showed no impact on entomologic indicators of transmission (Doannio et al. 1999).
Additionally, only two published studies report on the efficacy of Olyset® nets after two or more years of normal use (N'Guessan et al. 2001; Tami et al. 2004). Our studies represent the most rigorous attempt to date to validate the claims of two marketed LLINs for the prevention of malaria. The studies were well controlled, as all nets were subjected to the same conditions and criteria. All nets were tested until failure or 2 years after distribution. Each individual net was tested at regular intervals until biological activity dropped below a predetermined threshold, eliminating potential biases that might occur when sampling only a small number of nets still remaining in the field several years after distribution. We generated a large amount of data in both the laboratory and the field, all of which showed the Olyset® net to retain much of its original permethrin content after repeated washing or prolonged use. However, our data also indicated that little of the insecticide is available at the surface of the net fibres to contact and kill mosquitoes. We concluded that the Olyset® nets require heat-assisted regeneration – as originally recommended by the manufacturer – to maintain maximum efficacy.
We do not consider valid Dr Itoh's suggestions that our methods were biased against Olyset® in particular and permethrin-treated nets in general. In both our field and laboratory studies, significant reductions in mosquito mortality and knockdown (laboratory study only) by Olyset® were reversed when nets were regenerated according to the manufacturer's original instructions, suggesting that the cone assay was not affected either by the greater repellency afforded by permethrin or the possibility that the larger mesh size of Olyset® permitted mosquitoes to rest on the cardboard disc placed behind the net. Additionally, the nets treated with permethrin and a wash resistance process (the ‘cyclodextrin’ nets) performed better than conventional deltamethrin-treated nets in both the field and laboratory studies, again suggesting that the cone assay was not biased against permethrin-treated nets. Dr Itoh suggests several tests that may be better for evaluating LLINs, particularly the Olyset® net. While the cone test may be imperfect, the alternatives he suggests need considerable scrutiny before they can be considered as standard methods for measuring biological activity on netting. Although several substitutes for the cone test have been proposed, none has been directly compared with the WHO cone test against a range of insecticide-treated net products, including both conventional and long-lasting nets. In limited testing, we have found ball bioassays and tube tests (modified WHO susceptibility tests) to generate similar results to the cone bioassay when tested against Olyset® nets that have been washed repeatedly (Fig. 1).
We do not reject the Olyset® net as an LLIN. We recognize that its polyethylene fibres are far stronger than any polyester net currently on the market and its fibres clearly retain permethrin for several years. Our concern is that the insecticide is trapped within the fibres and unavailable to contact and kill mosquitoes. The data we presented clearly show little evidence for spontaneous regeneration of biological activity at temperatures that would be expected to be found inside homes in tropical climates and we concluded that heat-assisted regeneration is necessary to maximize the efficacy of the Olyset® nets. The nets originally provided to us by Sumitomo were packaged in clear plastic bags with instructions for the net to be placed in the bag after washing and left in the sun to regenerate its insecticidal activity. Although compliance with these instructions under normal use might be low, our data clearly suggest the need for such regeneration and we are unclear as to why these instructions were dropped.
We appreciate and understand the methodological difficulties in evaluation of LLINs, particularly the Olyset® net. However, we believe it is a dangerous precedent to allow each candidate LLIN to be considered a unique technology that cannot be evaluated by standard methods, particularly when the alternative methods have not been fully evaluated against a range of insecticide-treated net products. Our study of LLIN effectiveness under normal use conditions is one of the most rigorous in the literature. This study, when considered in the context of our laboratory experiments, shows that Olyset® does not regenerate as advertised under field conditions. We hope that Sumitomo will undertake to improve its product so that it fully reaches its life-saving potential.