The Physiology of Vasodilatation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68237/2/10.1177_000331976101200602.pd

To assess whether addition of pyriproxyfen to long-lasting insecticidal mosquito nets increases their durability compared to standard long-lasting insecticidal mosquito nets: study protocol for a randomised controlled trial

Background: The effectiveness of pyrethroid-treated bednets for malaria control in sub-Saharan Africa is under threat because of high levels of resistance to pyrethroid insecticides in the vectors. Here we assess the durability of polyethylene nets with a novel combination of permethrin, a pyrethroid, with pyriproxyfen, an insect juvenile mimic (PPF-LLIN), in comparison with a typical permethrin-treated long-lasting insecticidal net (LLIN). Methods: This is a cluster randomised controlled trial of net durability in Burkina Faso, with clustering at the level of the compound and includes entomological outcome measurements. Half the compounds in each village will be randomly allocated PPF-LLIN and half the LLIN. All sleeping places in a compound will be provided with one type of net. We will distribute the nets at the start of the first transmission season and follow net use at the start and end of each transmission season for 3 years. In one village, bio-efficacy and chemical content will be recorded immediately after net distribution and then at 6, 12, 18, 24, 30 and 36 months. In the other village net survivorship and fabric integrity will be recorded immediately after distribution, and then at 6, 12, 18, 24, 30 and 36 months. Routine measurements of indoor temperature and relative humidity will be made in both villages during the study. Residents will be followed for possible side effects of the PPF-LLIN by surveillance of known asthmatic subjects during the first month post-distribution and pregnancy outcomes will be monitored from antenatal clinic records. Discussion: The protocol is novel on two accounts. Firstly, it is the first to describe the procedure for measuring net durability following recent World Health Organisation (WHO) guidelines. Meeting the minimum requirements set in the guidelines is essential before a new type of net can be recommended by WHO’s Pesticide Evaluation Scheme (WHOPES). Secondly, it describes methods to monitor the persistence of an active ingredient that reduces vector fertility and fecundity. If the PPF-LLIN is both effective and persistent it will provide an alternative vector control strategy where pyrethroid-resistant vectors are present. Trial registration: ISRCTN30634670 webcite assigned 13 August 2014

The AvecNet Trial to assess whether addition of pyriproxyfen, an insect juvenile hormone mimic, to long-lasting insecticidal mosquito nets provides additional protection against clinical malaria over current best practice in an area with pyrethroid-resistant vectors in rural Burkina Faso: study protocol for a randomised controlled trial

Background: Recent reductions in malaria in sub-Saharan Africa have been associated with increased coverage with long-lasting insecticidal nets (LLINs). Pyrethroids are currently the only insecticide class used for treating nets, and the rapid increase in resistance to pyrethroids in vector mosquitoes may jeopardise future vector control. Nets containing a novel combination of permethrin, a pyrethroid, and pyriproxyfen, an insect juvenile hormone mimic, (PPF-LLIN) may enhance malaria control, as well as reducing the spread of pyrethroid-resistant mosquitoes. This trial will determine whether PPF-LLINs provide incremental protection against malaria over current best practice of LLINs and prompt treatment in an area with pyrethroid-resistant vectors. Methods: A 2 armed cluster-randomised controlled trial will be conducted in Burkina Faso to assess whether PPF-LLIN (containing 2% permethrin and 1% pyriproxyfen w/w) provide better protection against clinical malaria in children than 2% permethrin-treated LLINs. Study subjects will be recruited and provided with LLINs at the start of the study. The LLINs will be exchanged for PPF-LLIN by cluster in a step-wedge fashion so 3 months before the end of the 2 year trial all participants will have a PPF-LLIN. The primary endpoint will be clinical malaria incidence measured by passive case detection in a cohort of children, aged 6 months to 5 years. Anaemia and parasite prevalence will also be measured in children during cross-sectional surveys. Exposure to malaria parasites will be assessed using light traps followed by identification of common vector species and their sporozoite infection rates. Safety evaluation will include recording of adverse events and pregnancy outcomes. The main endpoint analysis will include adjusting for distance between village clusters with different types of nets, as the impact of PPF-LLIN is likely to increase as larger areas are dominated by PPF-LLIN, reducing the spill over of mosquitoes from villages with LLINs. Discussion: The step-wedge design is to measure the impact of an incrementally delivered environmental intervention where we expect the degree of control to be improved as more people use PPF-LLIN over a larger area. Trial findings will help inform policy makers on the effectiveness of PPF-LLIN nets for malaria control in areas of pyrethroid resistance. Trial registration: ISRCTN21853394 webcite – AvecNet, registered on 3 April 2013

Framework for rapid assessment and adoption of new vector control tools

Evidence-informed health policy making is reliant on systematic access to, and appraisal of, the best available research evidence. This review suggests a strategy to improve the speed at which evidence is gathered on new vector control tools (VCTs) using a framework based on measurements of the vectorial capacity of an insect population to transmit disease. We explore links between indicators of VCT efficacy measurable in small-scale experiments that are relevant to entomological and epidemiological parameters measurable only in large-scale proof-of-concept randomised control trials (RCTs). We hypothesise that once RCTs establish links between entomological and epidemiological indicators then rapid evaluation of new products within the same product category may be conducted through smaller scale experiments without repetition of lengthy and expensive RCTs