PermaNet® 3.0 - Efficacy Results

The working principle of PermaNet^® 3.0 is based on the synergistic effect of piperonyl butoxide (PBO) as demonstrated. This laboratory study was conducted to assess the bioefficacy of low and high concentrations of deltamethrin (DM) versus deltermetrin (DM) plus the synergist PBO against two strains of Aedes aegypti: one that was susceptible (Bora Bora) and one that was highly resistant to deltamethrin with multiple resistance mechanisms (Nha Trang)¹. The results were as shown in the graph below.

Mortality (%) of Ae. aegypti following exposure to net samples in 3-minute contact cone bioassays.

(Bingham et. al 2010)

The results indicate:

• ŸPBO alone had limited bioefficacy against both mosquito strains.
• ŸSusceptible mosquito strain: Deltamethrin alone at high concentration had high bioefficacy. The addition of PBO did not increase bioefficacy since it was already high.
• ŸResistant mosquito strain: Deltamethrin had limited bioefficacy. The addition of PBO significantly increased bioefficacy.

PermaNet^® 3.0 meets WHOPES efficacy criteria as an LLIN.

The World Health Organization pesticide evaluation scheme defines a long-lasting insecticidal net as one that is able to retain its biological activity against susceptible laboratory mosquitoes for at least 20 standard washes. In this case biological activity is measured as ≥95% knockdown and/or ≥80% mortality following 3-minutes exposure in cone bioassays². PermaNet^® 3.0 meets this criteria as it is able to rapidly regenerate fully within 24 hours and retains it biological activity for 20 washes, as seen in Tanzania where PermaNet^® 3.0 performed according to WHOPES standards at 0, 10 and 20 washes.

(Tungu et. al 2010)

In addition, study conducted in a semi-field experimental hut trial in an area with pyrethroid-susceptible vectors confirmed that PermaNet^® 3.0 also fulfills WHOPES criteria as a long-lasting insecticidal net. An experimental hut study conducted at a site in Muheza district in Tanzania³ with susceptible An. gambiae s.s. assessed the efficacy of PermaNet^® 3.0 versus the deltamethrin-only treated net (PermaNet^® 2.0) unwashed and washed 20 times. The results showed that PermaNet^® 3.0 retained its biological efficacy after 20 washes in comparison to the deltamethrin-only long-lasting insecticidal net.

(Tungu et. al 2010)

PermaNet^® 3.0 has demonstrable increased bioefficacy against pyrethroid-resistant malaria vectors.

Numerous experimental huts studies have examined the performance of versus mono-treated deltamethrin, permethrin long-lasting insecticidal nets in areas with documented insecticide resistance to local malaria vector species as shown in the table below.

Vietnam

*to deltamethrin (0.05%) or to permethrin (0.75%) in standard WHO susceptibility tests

Results of experimental huts studies with PermaNet® 3.0

Red shows the increase in efficacy with PermaNet^® 3.0 relative to mono-treated LLINs.

• Blood feeding inhibition: Both unwashed and washed 20 times PermaNet® 3.0 had enhanced blood feeding inhibition compared to mono-treated nets at all four sites.
• Insecticidal effect: Unwashed PermaNet^® 3.0 had enhanced insecticidal effect compared to the unwashed mono-treated nets at all four sites. Washed PermaNet^® 3.0 had enhanced insecticidal effect at two sites, and similar insecticidal effect at two sites compared to the washed mono-treated nets.

Increased efficacy of PermaNet^® 3.0 as an indicator of both community and individual protection

A mathematical model was used to estimate the impact of PermaNet^® 3.0 versus the mono-treated PermaNet^® 2.0 on malaria transmission levels assuming high net coverage (80% usage) and using published data from various experimental hut trials in Vietnam , Cameroon, Burkina Faso and Benin⁸. Across these four locations, the relative mean Entomological inoculation rate (EIR) value for PermaNet^® 3.0 compared to PermaNet^® 2.0 was 0.85 (i.e., 15% better protection). This was only when both nets were extensively washed and community protection was considered. When high coverage was modelled (80% use), the relative EIR was 0.61 (i.e., 39% better protection) regardless of whether or not the nets were washed. The overall conclusion is that in the pyrethroid-resistant areas studied, PermaNet^® 3.0 had a consistently better predicted impact than PermaNet^® 2.0.

Therefore, the result indicates that at high net coverage rates, PermaNet^® 3.0 could provide an overall increase in community and individual protection of up to 39%.

Conclusion Efficacy

• PermaNet® 3.0 meets WHOPES efficacy criteria as an LLIN.
• Data from experimental hut studies in areas with pyrethroid-resistant Anopheles demonstrate increased efficacy when compared to deltamethrin- or permethrin-only long-lasting insecticidal nets.
• At high net coverage rates, PermaNet^® 3.0 could provide an increase in community and individual protection of up to 39%.

Without waiting for control failures of vector control tools in areas with confirmed pyrethroid resistance in malaria vectors, programs should proactively consider deploying the use of PermaNet^® 3.0

References

1. Bingham et al 2011 Can piperonyl butoxide enhance the efficacy of pyrethroids against pyrethroidresistant Aedes aegypti?

2. WHO (2005) Guidelines for laboratory and field testing of long-lasting insecticidal mosquito nets. WHO/CDS/WHOPES/GCDPP/2005.11. World Health Organization, Geneva, Switzerland: 18pp.

3. Tungu et al 2011 Evaluation of PermaNet® 3.0 a deltamethrin-PBO combination net against Anopheles gambiae and pyrethroid resistant Culex quinquefasciatus mosquitoes: an experimental hut trial in Tanzania

4. Van Bortel W., et al. (2009) Impact of insecticide-treated nets on wild pyrethroid resistance Anopheles epiroticus population from southern Vietnam tested in experimental huts. Malaria Journal 8:248.

5. Adeogun A.O., et al. (In press)Village-scale evaluation of PermaNet® 3.0: an enhanced efficacy combination long-lasting insecticidal net against resistance populations of Anopheles gambiae s.s.

6. N'Guessan R., et al. (2011) An experimental hut evaluation of PermaNet® 3.0, a deltamethrin-piperonyl butoxide combination net, against pyrethroid-resistant Anopheles gambiae and Culex quinquefasciatus mosquitoes in southern Benin. Transactions of the Royal Society of Tropical Medicine and Hygiene 104:758-756.

7. Corbel V., et al. (2010) Field efficacy of a new mosaic long-lasting mosquito net (PermNet® 3.0) against pyrethroid resistant malaria vectors: a multi-centre study in Western and Central Africa. Malaria Journal 9:113.

8. Killeen G. F., et al. (2011) The importance of considering community-level effects when selecting insecticidal malaria vector control products. Parasites and Vectors 4:160.