Sterilising effects of pyriproxyfen on Anopheles arabiensis and its potential use in malaria control.

BACKGROUND: Insecticide resistance poses a major threat to current vector control campaigns. Insecticides with novel modes of action are therefore in high demand. Pyriproxyfen (PPF), a conventional mosquito pupacide, has a unique mode of action that also sterilises adult mosquitoes (unable to produce viable offspring) upon direct contact. However, the timing of PPF exposure in relation to when mosquitoes take a blood meal has an important impact on that sterilisation. This study investigated the relationship between different blood feeding and PPF exposure timings to determine the potential of PPF sterilisation in controlling Anopheles arabiensis. METHODS: Four treatment regimens were investigated: blood fed three days before PPF exposure (A), blood fed one day before PPF exposure (B), blood fed one day after PPF exposure (C) and blood fed three days after PPF exposure (D) for their impact on egg laying (fecundity) and the production of viable offspring (fertility), while the impact of PPF exposure on mosquito survival was investigated in the absence of a blood meal. All regimens and the survival study exposed mosquitoes to PPF via the bottle assay at 3 mg AI/m(2) for 30 minutes. RESULTS: Female mosquitoes that blood-fed one day prior to PPF exposure (regimen B), produced no viable offspring during that gonotrophic cycle (100% reduction in fertility). All other treatments had no significant effect. The observed reductions in fecundity and fertility were caused by the retention of eggs (97% of eggs retained, i.e. produced in the ovaries but not laid, in regimen B, p = 0.0004). Some of these retained eggs were deformed in shape. PPF exposure on mosquito survival in the absence of a blood meal was found to have no effect. CONCLUSIONS: The results presented here suggest that sterilising adult malaria vectors using PPF could form part of a malaria control strategy, taking advantage of the lack of reported resistance to PPF in mosquitoes and its unique mode of action. We propose that targeting resting mosquitoes, which are highly susceptible to PPF at low doses, is the optimal direction for developing this control tool

IDENTIFICATION OF KIF21A MUTATIONS AS A RARE CAUSE OF CONGENITAL FIBROSIS OF THE EXTRAOCULAR MUSCLES TYPE 3 (CFEOM3).

PURPOSE: Three congenital fibrosis of the extraocular muscles phenotypes (CFEOM1-3) have been identified. Each represents a specific form of paralytic strabismus characterized by congenital restrictive ophthalmoplegia, often with accompanying ptosis. It has been demonstrated that CFEOM1 results from mutations in KIF21A and CFEOM2 from mutations in PHOX2A. This study was conducted to determine the incidence of KIF21A and PHOX2A mutations among individuals with the third CFEOM phenotype, CFEOM3. METHODS: All pedigrees and sporadic individuals with CFEOM3 in the authors' database were identified, whether the pedigrees were linked or consistent with linkage to the FEOM1, FEOM2, and/or FEOM3 loci was determined, and the appropriate pedigrees and the sporadic individuals were screened for mutations in KIF21A and PHOX2A. RESULTS: Twelve CFEOM3 pedigrees and 10 CFEOM3 sporadic individuals were identified in the database. The structures of eight of the pedigrees permitted the generation of meaningful linkage data. KIF21A was screened in 17 probands, and mutations were identified in two CFEOM3 pedigrees. One pedigree harbored a novel mutation (2841G-->A, M947I) and one harbored the most common and recurrent of the CFEOM1 mutations identified previously (2860C-->T, R954W). None of CFEOM3 pedigrees or sporadic individuals harbored mutations in PHOX2A. CONCLUSIONS: The results demonstrate that KIF21A mutations are a rare cause of CFEOM3 and that KIF21A mutations can be nonpenetrant. Although KIF21A is the first gene to be associated with CFEOM3, the results imply that mutations in the unidentified FEOM3 gene are the more common cause of this phenotype