Bed nets containing the pyrethroid clofenpyr (CFP) and the pyrethroid piperonyl butoxide (PBO) are being promoted in endemic countries to improve the control of malaria transmitted by pyrethroid-resistant mosquitoes. CFP is a proinsecticide that requires activation by mosquito cytochrome P450 monooxygenase (P450), and PBO enhances the effectiveness of pyrethroids by inhibiting the action of these enzymes in pyrethroid-resistant mosquitoes. Thus, P450 inhibition by PBO may reduce the effectiveness of pyrethroid-CFP nets when used in the same home as pyrethroid-PBO nets.
Two experimental cockpit tests were conducted to evaluate two different types of pyrethroid-CFP ITN (Interceptor® G2, PermaNet® Dual) alone and in combination with pyrethroid-PBO ITN (DuraNet® Plus, PermaNet® 3.0). Entomological implications of use Pyrethroid resistance Vector populations in southern Benin. In both studies, all mesh types were tested in single and double mesh treatments. Bioassays were also conducted to assess drug resistance of vector populations in the hut and to study the interaction between CFP and PBO.
The vector population was sensitive to CFP but exhibited high levels of resistance to pyrethroids, but this resistance was overcome by pre-exposure to PBO. Vector mortality was significantly reduced in huts using a combination of pyrethroid-CFP nets and pyrethroid-PBO nets compared to huts using two pyrethroid-CFP nets (74% for Interceptor® G2 vs. 85%, PermaNet® Dual 57% vs. 83 % ), p < 0.001). Pre-exposure to PBO reduced the toxicity of CFP in bottle bioassays, suggesting that this effect may be due in part to antagonism between CFP and PBO. Vector mortality was higher in huts using combinations of nets containing pyrethroid-CFP nets compared to huts without pyrethroid-CFP nets, and when pyrethroid-CFP nets were used alone as two nets. When used together, mortality is highest (83-85%).
This study showed that the effectiveness of pyrethroid-CFP meshes was reduced when used in combination with pyrethroid-PBO ITN compared to use alone, whereas the effectiveness of mesh combinations containing pyrethroid-CFP meshes was higher. These results suggest that prioritizing the distribution of pyrethroid-CFP networks over other types of networks will maximize vector control effects in similar situations.
Insecticide-treated bed nets (ITNs) containing pyrethroid insecticides have become the mainstay of malaria control over the past two decades. Since 2004, approximately 2.5 billion insecticide-treated bed nets have been supplied to sub-Saharan Africa [1], resulting in an increase in the proportion of the population sleeping under insecticide-treated bed nets from 4% to 47% [2]. The effect of this implementation was significant. It is estimated that approximately 2 billion malaria cases and 6.2 million deaths were averted worldwide between 2000 and 2021, with modeling analyzes suggesting that insecticide-treated nets were a major driver of this benefit [ 2 , 3 ]. However, these advances come at a price: accelerated evolution of pyrethroid resistance in malaria vector populations. Although pyrethroid insecticide-treated bed nets may still provide individual protection against malaria in areas where vectors exhibit pyrethroid resistance [4], modeling studies predict that at higher levels of resistance, insecticide-treated bed nets will reduce epidemiological impact [5]. . Thus, pyrethroid resistance is one of the most significant threats to sustainable progress in malaria control.
Over the past few years, a new generation of insecticide-treated bed nets, which combine pyrethroids with a second chemical, has been developed to improve the control of malaria transmitted by pyrethroid-resistant mosquitoes. The first new class of ITN contains the synergist piperonyl butoxide (PBO), which potentiates pyrethroids by neutralizing detoxifying enzymes associated with pyrethroid resistance, particularly the effectiveness of cytochrome P450 monooxygenases (P450s) [6]. Bednets treated with fluprone (CFP), an azole insecticide with a new mechanism of action targeting cellular respiration, have also recently become available. Following the demonstration of improved entomological impact in hut pilot trials [7, 8], a series of cluster randomized controlled trials (cRCT) were conducted to evaluate the public health benefits of these nets compared with insecticide-treated nets using pyrethroids alone and provide the necessary evidence to inform policy recommendations from the World Health Organization (WHO) [9]. Based on evidence of improved epidemiological impact from CRCTs in Uganda [11] and Tanzania [12], the WHO endorsed pyrethroid-PBO insecticide-treated bednets [10]. The pyrethroid-CFP ITN was also recently published after parallel RCTs in Benin [13] and Tanzania [14] showed that the prototype ITN (Interceptor® G2) reduced the incidence of childhood malaria by 46% and 44%, respectively. 10]. ].
Following renewed efforts by the Global Fund and other major malaria donors to address insecticide resistance by accelerating the introduction of new bednets [15], pyrethroid-PBO and pyrethroid-CFP bednets are already being used in endemic areas. Replaces traditional insecticides. treated bed nets that use only pyrethroids. Between 2019 and 2022, the proportion of PBO pyrethroid mosquito nets supplied to sub-Saharan Africa increased from 8% to 51% [1], while PBO pyrethroid mosquito nets, including CFP pyrethroid mosquito nets , “dual action” mosquito nets are expected to account for 56% of shipments. Enter the African market by 2025[16]. As evidence of the effectiveness of pyrethroid-PBO and pyrethroid-CFP mosquito nets continues to grow, these nets are expected to become more widely available in the coming years. Thus, there is a growing need to fill information gaps regarding the optimal use of new generation insecticide-treated bed nets to achieve maximum effect when scaled up for full operational use.
Given the concurrent proliferation of pyrethroid CFP and pyrethroid PBO mosquito nets, the National Malaria Control Program (NMCP) has one operational research question: Will its effectiveness be reduced – PBO ITN? The reason for this concern is that PBO acts by inhibiting mosquito P450 enzymes [6], whereas CFP is a proinsecticide that requires activation through P450s [17]. Therefore, it is hypothesized that when pyrethroid-CFP ITN and pyrethroid-CFP ITN are used in the same home, the inhibitory effect of PBO on P450 may reduce the effectiveness of pyrethroid-CFP ITN. Several laboratory studies have shown that pre-exposure to PBO reduces the acute toxicity of CFP to mosquito vectors in direct exposure bioassays [18,19,20,21,22]. However, when conducting studies between different networks in the field, the interactions between these chemicals will be more complex. Unpublished studies have examined the effects of using different types of insecticide-treated nets together. Thus, field studies assessing the impact of using a combination of insecticide-treated pyrethroid-CFP and pyrethroid-PBO bed nets in the same household will help determine whether potential antagonism between these types of nets poses an operational problem and help determine the best strategy deployment. for its uniformly distributed regions.
Post time: Sep-21-2023