Comparison Trial Between Two Repellent Products and a Positive Control Against Culicoides Nubeculosus Midges

Mosquitoes, midges and other biting insects are vectors of extremely important diseases such as malaria, yellow fever, filariasis and many viruses and also may be of great nuisance value. The use of repellent products can provide added personal protection from disease transmission and nuisance bites. New effective repellents would offer an additional option for protection against biting insects. The aim of this study is to determine the effectiveness of two topically applied insect repellent products provided and one positive control against Culicoides nubeculosus. Culicoides nubeculosus is a common species of biting midges belonging to the family Ceratopogonidae. Culicoides midges are small biting flies found throughout the world, breeding primarily in moist, damp, muddy habitats. To develop their eggs, female Culicoides require a blood meal from warm-blooded vertebrates, most often a domesticated animal and humans. Culicoides are implicated in the transmission of multiple zoonotic diseases, such as bluetongue virus, African horse sickness, and bovine ephemeral fever, and their bites can be painful and can cause uncomfortable irritation to both humans and livestock.

This is a single-centre, single-arm study with all participants testing two formulations containing PMD and a positive control product containing Picaridin. The control for each test is an untreated arm. There is no blinding or randomisation employed, since the outcome measures are based on midge behaviour. Repellent product testing takes place in a laboratory setting using 7 participants (preferably gender balanced). Each participant will test both PMD formulations and a positive control product.

Volunteers will be consented prior to any screening procedures being undertaken. Volunteers who do not meet the criteria for eligibility will be excluded. In order to assess sensitivity in those volunteers who claim not to be sensitive to insect bites, volunteers will be given a bite test using the midge species used for testing. Participants can stop at any time without giving a reason for withdrawing. Data collected to the point of withdrawal will be used in the analysis of the study, unless the participant requests that their data is not used, in which case it will be removed from the database. Participants may also be removed at the discretion of the Chief Investigator, where continued participation may affect the safety of the participant or where there is a development of any condition which might interfere with study participation.

All adverse events and serious adverse events should be reported. Any questions concerning adverse event reporting should be directed to the chief investigator in the first instance.

The midges will be obtained from insecticide-susceptible reference strains held at the Pirbright Institute (Institute for Animal Health). They will be maintained at 22-24°C, 80-90% relative humidity, with a 12:12 hour photoperiod. Female midges will be host-seeking, of uniform age and 3-8 days post-emergence. Active host-seeking females will be selected to ensure a good response from the test midges using an aspirator or an appropriate airflow apparatus. Before the start of each test, the participant will insert a bare (control) left arm into the cage for 1 minute to assess biting activity of the midges. Only cages with at least 10 midges landing within one minute will be used in the tests. This same procedure is used to assess whether volunteers are attractive to the midges. The number of midges probing or biting the arm after 1 minute will be counted and recorded (to provide biting rate data of the control test for the Protective Efficacy endpoint) and the arm removed from the cage. Immediately after, the right (treated) arm is inserted into the cage for 1 minute. The number of midges probing or biting the arm after 1 minute will be counted and recorded. A further hour post-application of the repellent product, the left arm (control) of the volunteer is again inserted into the cage. The number of midges probing or biting the arm after 1 minute will be counted and recorded and the arm removed from the cage. If less than 10 midges land on the untreated arm during this 1 minute test the cage will be refreshed with new midges and the test repeated. Immediately after, the right (treated) arm is again inserted into the cage for 1 minute. The number of midges probing or biting the arm after 1 minute will be counted and recorded. This procedure will be repeated at hourly intervals throughout the test.