Product description:
This generic product specification is for a long lasting insecticide treated net to improve malaria (and dengue) vector control in the Disease Endemic Countries (DECs).
The product must fulfil the WHOPES criteria for long lasting insecticidal nets:
- Retention of activity of biological activity in WHO cone bioassay tests or tunnel tests for at least 20 standardised washes under laboratory conditions.
- At Phase 2 (small-scale field trials in experimental huts), the LLIN should perform equal or better after at least 20 washes than a conventionally treated net when washed till just before exhaustion. (defined as the last wash for which the net still gives ≥ 80 % mortality or ≥95% knockdown)
- At Phase 3 (large-scale field trials), after 3 years of field use in domestic situations, at least 80% of sampled nets should meet minimum performance criteria as indicated by 80% mortality in WHO cone bioassay tests or tunnel tests.
This specification is aimed at providing long lasting insecticidal nets that can withstand 3 years in use and still provide protection against mosquito borne malaria.
These criteria may be revised by WHO as further evidence of LLIN field effectiveness is obtained and new types of LLIN come onto the market.
WHOPES currently recommend 3 different pyrethroid treated long lasting insecticidal nets, based on permethrin, deltamethrin and alphacypermethrin. They are in the process of evaluating 3 further pyrethroid treated long lasting nets based on alphacypermethrin, lambda cyhalothrin and deltamethrin. In view of this and the mounting evidence of the development of pyrethroid resistance in West Africa (N’Guessan et al., 2007) the IVCC will target the development of non pyrethroid and bi-treated (containing at least one non pyrethroid active ingredient) long lasting insecticidal nets.
Essential Product Characteristics:
Performance and Efficacy:
Fulfilment of WHO criteria for a LLIN: Performance criteria required by WHOPES in terms of wash resistance and efficacy to obtain approval as an LLIN are
- At Phase 1 (laboratory), retention of biological activity in WHO cone bioassay tests or tunnel tests for at least 20 standardised washes under laboratory conditions.
- At Phase 2 (small-scale field trials in experimental huts), the LLIN should perform equal or better than a conventionally treated net when washed till just before exhaustion.
- At Phase 3 (large-scale field trials), after 3 years of field use in domestic situations, at least 80% of sampled nets should meet minimum performance criteria as indicated by 80% mortality in WHO cone bioassay tests or tunnel tests.
These performance criteria should be passed for both susceptible and pyrethroid resistant strains:
The performance criteria are established using standard pyrethroid susceptible mosquito strains as well as pyrethroid resistant strains containing either kdr or metabolic resistance as test insects.
The WHO criteria were established for pyrethroid-based LLIN at a time when pyrethroids were known to be very effective against field strains of malaria vectors. If the point is reached at which pyrethroid treated nets fail to provide sufficient levels of protection, it may be necessary to change the criteria of what is an acceptable level of performance in a non-pyrethroid treated net. The criteria outlined above are ideal criteria based on the known performance of a good LLIN against susceptible mosquitoes. A bitreated net that simply works better than a pyrethroid LLIN against resistant mosquitoes has to be taken seriously even if for example, it does not perform up to 20 washes..
No cross resistance to pyrethroids Such resistance exists at low frequency in some areas and is common in others.
Cost of implementation in the field:
It is a prerequisite of the global access plan that the product should be affordable and competitively priced for target populations in disease endemic countries. The health economics cost/benefit assessment would take into consideration not only the cost of the product but its cost-effectiveness in reducing malaria/dengue (as shown in phase III trials), the much longer residual activity and reduced operational costs, and its capacity to stop resistance being selected.
The product will be benchmarked against the current costs for other LLIN’s on the market. This will be reviewed at all key milestones within all projects.
Safety and regulatory profile:
Must meet WHOPES risk assessment standards for LLIN’s:
An initial positive WHO generic risk assessment for insecticidal nets (WHO/CDS/WHOPES/GCDPP/2004.6/WHO/PCS/04.1)for the active ingredients must be submitted with the proposal for review and comment by the IVCC ESAC toxicology, eco-toxicology and risk assessment professionals.
A full standard regulatory package will be developed for the long lasting insecticidal nets once the formulation technology is confirmed. As part of this package information on the efficacy, safety and acceptability of the product shall be submitted in accordance with the WHO ‘Guidelines for testing mosquito adulticides for indoor residual spraying and treatment of mosquito nets. (WHO/CDS/NTD/WHOPES/GCDPP/2006.3.’) The dossier will be submitted to the appropriate regulatory authority, including WHOPES, for registration against internationally accepted criteria.
Regulatory status:
The active ingredients used must be registered for use in at least one major regulatory authority (EPA, EU or Japan) for a crop protection or vector control application.
Suitability for end users:
LLINs are widely accepted in DEC as an effective means of protecting against malaria. The LLIN shall retain the characteristics of a pyrethroid LLIN against susceptible mosquitoes but the additional activity against resistant insects will improve further the product’s acceptability and suitability to end users.
Manufacturing considerations:
The final LLIN needs to be suitable for manufacture in an existing manufacturing plant. The active ingredients need to be freely available to the company developing the product.
IP issues:
There should be freedom to operate from any existing patent. All background and foreground IP should be freely made available for the products development and use in vector control in disease endemic countries.
Desirable product characteristics
Demonstrates efficacy against nuisance mosquitoes (culicines)
Demonstrates Inhibition of entry into houses
Synergy demonstrated between the active ingredients in bi-treated nets
Resistance to handling and wear, and retention of efficacy