Correction to: Assessing the impact of the addition of pyriproxyfen on the durability of permethrin-treated bed nets in Burkina Faso: a compound-randomized controlled trial.

An amendment to this paper has been published and can be accessed via the original article.

Assessing the impact of the addition of pyriproxyfen on the durability of permethrin-treated bed nets in Burkina Faso: a compound-randomized controlled trial.

BACKGROUND: Long-lasting insecticidal nets (LLINs) treated with pyrethroids are the foundation of malaria control in sub-Saharan Africa. Rising pyrethroid resistance in vectors, however, has driven the development of alternative net formulations. Here the durability of polyethylene nets with a novel combination of a pyrethroid, permethrin, and the insect juvenile hormone mimic, pyriproxyfen (PPF), compared to a standard permethrin LLIN, was assessed in rural Burkina Faso. METHODS: A compound-randomized controlled trial was completed in two villages. In one village 326 of the PPF-permethrin nets (Olyset Duo) and 327 standard LLINs (Olyset) were distributed to assess bioefficacy. In a second village, 170 PPF-permethrin nets and 376 LLINs were distributed to assess survivorship. Nets were followed at 6-monthly intervals for 3 years. Bioefficacy was assessed by exposing permethrin-susceptible and resistant Anopheles gambiae sensu lato mosquito strains to standard World Health Organization (WHO) cone and tunnel tests with impacts on fertility measured in the resistant strain. Insecticide content was measured using high-performance liquid chromatography. LLIN survivorship was recorded with a questionnaire and assessed by comparing the physical integrity using the proportionate hole index (pHI). RESULTS: The PPF-permethrin net met WHO bioefficacy criteria (≥ 80% mortality or ≥ 95% knockdown) for the first 18 months, compared to 6 months for the standard LLIN. Mean mosquito mortality for PPF-permethrin nets, across all time points, was 8.6% (CI 2.6-14.6%) higher than the standard LLIN. Fertility rates were reduced after PPF-permethrin net exposure at 1-month post distribution, but not later. Permethrin content of both types of nets remained within the target range of 20 g/kg ± 25% for 242/248 nets tested. The pyriproxyfen content of PPF-permethrin nets declined by 54%, from 10.4 g/kg (CI 10.2-10.6) to 4.7 g/kg (CI 3.5-6.0, p < 0.001) over 36 months. Net survivorship was poor, with only 13% of PPF-permethrin nets and 12% of LLINs still present in the original household after 36 months. There was no difference in the fabric integrity or survivorship between the two net types. CONCLUSION: The PPF-permethrin net, Olyset Duo, met or exceeded the performance of the WHO-recommended standard LLIN (Olyset) in the current study but both net types failed the 3-year WHO bioefficacy criteria.

The recent escalation in strength of pyrethroid resistance in Anopheles coluzzi in West Africa is linked to increased expression of multiple gene families.

BACKGROUND: Since 2011, the level of pyrethroid resistance in the major malaria mosquito, Anopheles coluzzi, has increased to such an extent in Burkina Faso that none of the long lasting insecticide treated nets (LLINs) currently in use throughout the country kill the local mosquito vectors. We investigated whether this observed increase was associated with transcriptional changes in field-caught Anopheles coluzzi using two independent whole-genome microarray studies, performed in 2011 and 2012. RESULTS: Mosquitoes were collected from south-west Burkina Faso in 2011 and 2012 and insecticide exposed or non-exposed insects were compared to laboratory susceptible colonies using whole-genome microarrays. Using a stringent filtering process we identified 136 genes, including the well-studied detoxification enzymes (p450 monoxygenases and esterases) and non-detoxification genes (e.g. cell transporters and cuticular components), associated with pyrethroid resistance, whose basal expression level increased during the timeframe of the study. A subset of these were validated by qPCR using samples from two study sites, collected over 3 years and marked increases in expression were observed each year. We hypothesise that these genes are contributing to this rapidly increasing resistance phenotype in An. coluzzi. A comprehensive analysis of the knockdown resistance (kdr) mutations (L1014S, L1014F and N1575Y) revealed that the majority of the resistance phenotype is not explained by target-site modifications. CONCLUSIONS: Our data indicate that the recent and rapid increase in pyrethroid resistance observed in south-west Burkina Faso is associated with gene expression profiles described here. Over a third of these candidates are also overexpressed in multiple pyrethroid resistant populations of An. coluzzi from neighbouring Côte d'Ivoire. This suite of molecular markers can be used to track the spread of the extreme pyrethroid resistance phenotype that is sweeping through West Africa and to determine the functional basis of this trait.

Increased pyrethroid resistance in malaria vectors and decreased bed net effectiveness, Burkina Faso.

Malaria control is dependent on insecticides. Increases in prevalence of insecticide resistance in malaria vectors across Africa are well-documented. However, few attempts have been made to quantify the strength of this resistance and link it to the effectiveness of control tools. Using quantitative bioassays, we show that in Burkina Faso pyrethroid resistance in Anopheles gambiae mosquitoes has increased in intensity in recent years and now exceeds 1,000-fold. In laboratory assays, this level of resistance renders insecticides used to impregnate bed nets ineffective. Thus, the level of personal and community protection afforded by long-lasting insecticide-treated net campaigns will probably be reduced. Standardized methods are needed to quantify resistance levels in malaria vectors and link these levels to failure of vector control methods.