A novel mosquito net that combines the pyrrole chlorfenapyr and the pyrethroid alpha-cypermethrin represents a breakthrough in the development of Long Lasting Insecticidal Nets (LLINs) to control pyrethroid resistant mosquitoes.
A novel mosquito net that kills insecticide resistant mosquitoes which would normally survive exposure to standard pyrethroid treated nets marks a breakthrough in the development of new long-lasting nets that can meet the challenge of malaria control in countries in areas of high insecticide resistance, reports a new study published in Plos One. The project was a partnership between IVCC, the London School of Hygiene & Tropical Medicine, the West African vector control trial site (CREC) in Benin, which together with the chemical company BASF SE, have developed and evaluated a new type of long lasting net, Interceptor® G2.
LLINs that kill the Anopheline mosquitoes which transmit malaria are the simplest and most widely used method to prevent the disease. The World Health Organization (WHO) estimates that over half the population of sub-Saharan Africa now sleeps under LLIN and this has helped to reduce malaria cases by a third and mortality rates by two thirds over the last 15 years.
Until recently, the LLIN technology has been wholly dependent on pyrethroids as the only class of insecticide safe to use on LLIN. The rapid spread of resistance to these insecticides in malarial mosquitoes threatens further progress unless new types of insecticide which are both effective and safe can be developed. Professor Mark Rowland and Dr Raphael N’Guessan of the London School of Hygiene & Tropical Medicine anticipated this problem over 13 years ago. It was discussed with BASF to repurpose an insecticide which previously had been used to control termites and pests from indoor areas including commercial kitchens.
Mark Rowland said: “Back then we knew that selection of resistance to pyrethroids in malarial mosquitoes was only a question of time. The challenge was to identify a suitable insecticide that had right combination of residual efficacy against insects, low water solubility, no cross resistance to other classes of insecticide and was safe to use on nets. Chlorfenapyr, a pyrrole insecticide, seemed to have that rare collection of attributes and we started working with BASF. A few years later BASF and LSHTM had demonstrated chlorfenapyr’s potential in bioassay, subjected it to WHO toxicological risk assessment, and completed the first experimental hut trials, small-scale studies under house-like conditions in West and East Africa”.
In 2011, BASF entered into full partnership with IVCC and set its sights on developing a long lasting insecticidal net which would combine chlorfenapyr and the pyrethroid alpha-cypermethrin.
Dr Susanne Stutz, the BASF Project Manager, said: “Even then it was not plain sailing. Chlorfenapyr would simply not behave predictably in laboratory bioassay. However, when applied to nets and testing in experimental hut trials, chlorfenapyr would always kill mosquitoes that made contact with the netting. The explanation lies in the chlorfenapyr’s unique mode of action. Unlike standard public health insecticide which are neurotoxic, chlorfenapyr disrupts cellular respiratory pathways and is most toxic to mosquitoes which are active at night when they make contact with the net”.
The target product profile set by BASF and IVCC was a chlorfenpyr / alpha-cypermethrin mixture long-lasting insecticidal net that would remain effective against pyrethroid resistant mosquitoes after 20 standardised washes, a threshold established by WHO for all LLIN. Four years later, Interceptor® G2, has fulfilled its initial promise and in experimental hut trials killed over 70% of pyrethoid-resistant Anopheles gambiae when the standard pyrethroid LLIN killed only 20%. The long lasting formulation retained insecticidal activity on the net after 20 standardized washes in soap solution.
Raphael N’Guessan, the scientist who managed the trials in West Africa said: “The unique mode of action of chlorfenapyr means that insecticide resistance based on target site insensitivity in the insect nervous system and other mechanisms shows no cross resistance to chlorfenapyr. The mosquito mortality rates generated by Interceptor® G2 are similar to the rates generated by standard pyrethroid LLIN 10 years ago when most mosquitoes were fully susceptible to pyrethroids”
This publication marks the first of several trials of Interceptor® G2 carried out in African trial sites in Benin, Ivory Coast, Burkina Faso and Tanzania. BASF has submitted the Interceptor® G2 dossier to the WHO Pesticide Evaluation Scheme for interim recommendation expected in March 2017.
David Malone, IVCC Technical Manager, said: “Africa has become a net using culture. Insecticide treated nets are the most important tool we have to prevent malaria. This new technology demonstrates that insecticide treated nets will continue to be an essential weapon in the fight against malaria in the future despite pyrethroid resistance.”
The development and evaluation of Interceptor® G2 is the result of partnership between the BASF SE of Germany, the London School of Hygiene & Tropical Medicine, and IVCC.
The full publication can be found at Plos One:
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165925
Science Magazine this month (October 2016) features an excellent article about the work of IVCC and Liverpool School of Tropical Medicine (LSTM) in fighting insecticide resistance in mosquitoes.
The article, by Science contributing correspondent Kal Kupferschmidt, highlights the threat to malaria reduction by growing insecticide resistance. It points to the critical work of IVCC and LSTM in ‘evaluating new weapons to fight mosquitoes’. LSTM does this through its vector biology programmes, and IVCC through working with industrial agrochemical giants to create innovate new insecticides that will combat insecticide resistance.
IVCC’s CEO, Nick Hamon, emphasises the challenge of keeping industrial companies engaged in developing new insecticides when the potential market for new public health insecticides is small. The future is hopeful, however, as he points out three potential new insecticides will shortly be moved into the final testing stages.
Read the full article here:
Still Time to Battle Insecticide Resistance 22nd November 2016Insecticide treated bednets are highly effective at reducing malaria transmission, despite the rise in insecticide resistance, according to a study carried out by the WHO. But this is not grounds for complacency, according to the President of the American Society of Tropical Medicine and Hygiene, Dr Stephen Higgs. ‘This study provides encouraging news that we have not yet run out of time in battling insecticide resistance’, he said. ‘However, we must take advantage of the time we now have to invest in research, and generate new tools that will allow us to finally defeat this complex and challenging disease.’
The WHO research across five countries showed that people who slept under a long-lasting insecticide treated net (LLIN) had significantly lower rates of malaria infection than those who did not use a net. This was consistent with recent research conducted by the Centers for Disease Control and Prevention (CDC) which showed that insecticide treated bednets provided significant protection to children in an area of Malawi with considerable malaria transmission and low levels of insecticide resistance. The research found that the insecticide treated bednets still kill mosquitos even in areas where there is known resistance.
Dr Pedro Alonso, Director of the WHO Global Malaria Programme said that the key finding of the study is that treated nets continue to be a highly effective tool in the malaria fight. ’The study supports WHO’s call for achieving universal coverage of long-lasting insecticide treated bednets for all populations at risk of malaria,’ he said.
According to the WHO World Malaria Report 2015, mosquito nets have been the most important malaria control tool in sub-Saharan Africa, accounting for an estimated 69% of cases prevented through interventions since 2001. Since 2000, malaria case incidence has declined by 37% globally and malaria death rates have fallen by 60%. In sub-Saharan Africa, the region most heavily affected by malaria, cases and deaths have fallen by 42% and 66%, respectively.
Following the study Dr Alonso has called for a global strategy for comprehensive control of disease carrying insects to be high on the agenda for the 2017 World Health Assembly. He said there is a growing need for sustainable approaches supported by enhanced expertise to aid the fight against malaria and other insect-borne diseases. WHO continues to highlight the urgent need for new and improved malaria-fighting tools to accelerate progress towards global elimination goals and is calling for greater investments in vector control interventions, improved diagnostics and more effective medicines.
IVCC is at the forefront of the fight against disease carrying insects. Intensive research since 2005, with global leaders in insecticide development, has produced a promising pipeline of new anti-mosquito tools currently under development. WHO is revising its process for reviewing and recommending new malaria vector interventions in order to fast track their route to the field.
Mosquito Resistance a Growing Concern, says WHO 23rd November 2016Mosquito resistance to insecticides remains a growing concern, according to WHO estimates revealed at the American Society of Tropical Medicine and Hygiene meeting in Atlanta recently.
WHO reports 60 countries have recorded mosquito resistance to at least one of the four insecticides used in long-lasting insecticide treated nets (LLINS) and indoor residual spraying (IRS) since 2010. Of these, 49 countries have reported resistance to two or more insecticide classes. WHO says that if resistance continues to intensify, the mosquito-killing capacity of LLINs and indoor residual spraying may steadily weaken.
This would be a tragedy for sub-Saharan Africa where acclaimed research last year demonstrated that LLINs accounted for about 78% of the substantial malaria gains over the past 15 years or so. (Read more about this here.)
If the battle against malaria is to continue to drive back this scourge from sub-Saharan Africa, the need to continue to develop new public health insecticides is paramount. Fortunately, due to the foresight of leading vector science academics who saw the potential threat over 15 years ago, the Bill & Melinda Gates Foundation and other forward thinking funders have invested appropriately in the search for new public health insecticides. IVCC was established in 2005 as the only vector control focused Product Development Partnership (PDP) and has worked closely with world-leading vector scientists and agro-chemical companies to design and develop novel public health insecticides targetted precisely at killing the mosquitoes that transmit malaria.
Professor Hilary Ranson, one of the world’s leading authorities on insecticide resistance, warned earlier this year that pyrethroid resistance is the biggest biological threat to malaria control in Africa. (Read about this here.) Together with other leading specialists in this area she says that the urgent need for new vector control products is apparent, and the new vector control products that are in the pipeline must be rationally deployed in order to slow down future resistance developing.
IVCC has a healthy pipeline of novel vector control tools, itself a product of consistent commitment by public health funders and industrial partners to finding a solution to the global threat of insect-transmitted diseases.
*The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. S Bhatt, et al.
WHO World Malaria Report 2016 Highlights Key Role of Vector Control 14th December 2016Despite growing mosquito resistance to insecticides, vector control remains the main way of preventing and reducing malaria transmission, says the WHO in its recently released World Malaria Report 2016.
‘Long-lasting insecticidal nets are the mainstay of malaria prevention’, said Secretary General, Margaret Chan, adding that the WHO recommends their use for all people at risk of malaria. ‘Across sub-Saharan Africa, the proportion of people sleeping under treated nets has nearly doubled over the last 5 years’, she said.
The report spotlights a number of positive trends, particularly in sub-Saharan Africa, the region that carries the heaviest malaria burden. It shows that, in many countries, access to disease-cutting tools is expanding at a rapid rate for those most in need.
Although excellent progress has been made, in 2015 there was still a global tally of 212 million cases of malaria and 429 000 deaths. Gaps in coverage are reported for key interventions such as bed nets and in-door residual spraying, with around 43% of the population in sub-Saharan Africa still unprotected.
The progress of the past 15 years is threatened by the rapid development and spread of mosquito resistance to insecticides. Antimalarial drug resistance could also jeopardize recent gains.
Welcoming the Report, IVCC CEO, Dr Nick Hamon said, ‘The significant gains in the battle against malaria are to be applauded, but the battle is far from over. Vector control is now widely recognised as a key player in the battle and IVCC is deeply committed to ensuring it delivers the new vector control tools needed to ultimately defeat this insidious disease.’
Find out more about the World Malaria Report 2016 here.