Malaria mortality rates are estimated to have declined globally by 60% between 2000 and 2015. One of the major factors responsible for this decline was the distribution and use of bednets treated with pyrethroid–based insecticides.
Insecticide-treated bednets were originally pioneered by a team based in Muheza, Tanzania, in the 1980s (see a blog by Jo Lines) and championed by the late Professor Chris Curtis. Nets were treated by washing them in a pyrethroid solution, but these nets needed re-treating frequently. Long lasting insecticide treated bednets (LLINs), in which insecticide has been incorporated directly into the polypropylene or polyethylene fabric that the nets are made of, have been developed by many companies, and mass distribution programmes have been in operation since the beginning of this century.
LLINs both repel mosquitoes and kill those that land on the nets. Many studies demonstrated the decline in mosquito populations when LLINs were deployed (for example this study in Kenya), and their use had been associated with protection against malaria. However, there is a problem.
Pyrethroid resistance
The rapid spread of resistance to pyrethroids has given rise to concerns that the effectiveness of LLINs will decline. This has led to a search for other insecticides that are still effective, and are also safe for humans to be exposed to at close quarters. Investigations are now underway to assess the effectiveness of incorporating an additional insecticide into the fabric that LLINs are made of.
One of these insecticides under investigation is pyriproxyfen (PPF).
It is a juvenile hormone analog that acts as an insect growth regulator that adversely affects mosquito reproduction. Thus, it has a different mode of action to the pyrethroids. Previous trials have shown that, when this insecticide is incorporated into bed nets with permethrin (trade name Olyset Duo), mortality and blood feeding activity of pyrethroid-resistant mosquitoes was reduced more successfully than permethrin-only treated nets, and mosquitoes that survived an encounter with these nets did not produce offspring.
A more extensive comparison of these two types of nets, assessing both entomological parameters and the incidence of clinical malaria in infants sleeping under the nets, has now been carried out in Burkina Faso.
Malaria in Burkina Faso
In 2014 it was reported that 22% of deaths in medical centres in Burkina Faso were due to malaria; well over half of these were infants. This followed four years of mass distribution of ILLNs, reaching approximately 90% of households. This report concluded that poor installation of nets and insufficient provision per household contributed to the incidence of malaria remaining high. Between 2015 and 2016 the situation deteriorated and there was an increase in cases of malaria in infants.
The authors of a study, recently published in The Lancet, suggested a third problem. Vectors of malaria in Burkina Faso are now highly resistant to the pyrethroids used to treat ILLNs, making them much less effective. This may be a major factor in the reversal of the decline in malaria cases. They have undertaken a comparison of the effectiveness of PPF- treated nets (Olyset Duo) compared with standard nets (Olyset) The study took place in the south west of Burkina Faso, an area with high levels of malaria transmission.
The study
The study involved incremental replacement of standard ILLNs with nets incorporating the insecticide combination and took place over a period of two years.
Fifty infants in each of forty clusters of villages were monitored for incidence of clinical malaria by passive case detection (attendance at hospital with a fever) and during four cross-sectional studies, when they were visited at home. Mosquito densities were estimated using collections made with indoor light traps hanging near a bednet-protected bed. Mosquitoes were checked for the presence of infective stage (sporozoites) malaria parasites and ovaries examined to determine whether they had laid a batch of eggs previously, as a proxy for age determination.
Most mosquitoes caught in the light traps were anopheline, malaria transmitting, mosquitoes. There were 22% fewer mosquitoes in traps close to PPF-treated nets and far fewer of these contained sporozoites and/or had previously produced eggs than nets treated with permethrin alone. This resulted in a decline in the number of infective bites per season (the entomological inoculation rate) from 85 associated with the standard nets, to 42 with the Olyset Duo nets.
Infants sleeping under Olyset Duo nets were 52% less likely to be anaemic and 12% less likely to have clinical malaria, a finding attributed to the reduction in mosquito numbers. However, examination of blood taken from infants in the two groups did not show a measurable effect on the number of children with parasites in their blood, probably because the entomological inoculation rate in the group with PPF-treated nets was still so high and because parasites may have persisted in the blood from before the time the trial started.
What’s next?
The authors of the study recognised the complexity of the action of the Olyset Duo nets and confounding factors that may have affected the conclusions of this trial. They suggest that future studies should trial nets with mixtures of insecticides that do not include pyrethroids at all.
Even though an intact net without holes still provides a barrier to access to sleeping individuals, the potential decline in the added benefit of pyrethroid-treated nets in areas where insecticide resistance is high is worrying. New formulations will undoubtedly give ILLNs a new lease of life in these areas, but they will not counter another problem associated with their use; the evolution of changes in mosquito biting behaviour associated with ILLN use, whereby peak time and place of biting changes and people become more vulnerable when they are not sleeping under nets (discussed in a recent BugBitten blog).
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