A Clinical Study to Develop an Uninfected Sand Fly Biting Protocol

This is a healthy-volunteer clinical study to develop a sand fly biting protocol. 12 participants will be recruited for the study. It is an open-label randomized clinical study with 2 arms (for 2 different species of sand fly: Phlebotomus papatasi and Phlebotomus duboscqi). Participants will be randomized to each arm with 6 participants in each arm. This study will take place at the Translational Research Facility (Q Block), Hull York Medical School & Department of Biology, University of York, York.

The participants will be followed up to 21 days post-sand fly bite. There will then be a focus group once all participants have completed their follow-up.

Inclusion criteria

• Healthy adults aged 18 to 65 years on the day of screening
• Willing and able to give written informed consent
• Willing to undergo an Hepatitis B, Hepatitis C & HIV test
• Willing to undergo a pregnancy test during screening and follow-up visits and must not be breastfeeding (female volunteers)
• Willing to refrain from blood donation during the study
• Using a reliable and effective form of contraception (female volunteers)
• Judged, in the opinion of a medically qualified Clinical Investigator, to be able and likely to comply with all study requirements as set out in the protocol
• Without any other significant health problems as determined by medical history, physical examination, results of screening tests and the clinical judgment of a medically qualified Clinical Investigator
• Available for the duration of the study
• Willing to refrain from travel to regions where Leishmania-transmitting sand flies are present, from recruitment until the last study visit.
• Willing to consent to a report from the volunteer's GP (General Practitioner) confirming medical eligibility, to be provided before study entry

Exclusion criteria

The volunteer may not enter the study if any of the following apply:

• Receipt of a live attenuated vaccine within 30 days or other vaccine within 14 days of screening
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned study.
• History of allergic disease/atopy or reactions or a history of severe or multiple allergies to drugs or pharmaceutical agents
• Any significant chronic skin condition as judged by the medical team
• Any history of Leishmaniasis
• Any history of travel within the last 30 days to regions where Leishmania major-transmitting sand flies are endemic*.
• Any past history of more than 30 contiguous days stay in regions where Leishmania major-transmitting sand flies are endemic*.
• Any history of severe local or general reaction to insect bites, defined as
• Local: extensive, indurated redness and swelling involving most of the antero-lateral thigh or the major circumference of the arm, not resolving within 72 hours
• General: fever ≥ 39.5°C within 48 hours, anaphylaxis, bronchospasm, laryngeal oedema, collapse, convulsions or encephalopathy within 48 hours
• Any history of anaphylaxis Females - pregnancy, less than 12 weeks postpartum, lactating or willingness/intention to become pregnant during the study and for 3 months following the study.
• Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis
• Total IgE levels >81 Kilo-units/L Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months
• Tuberculosis, leprosy, or malnutrition
• Any chronic illness requiring hospital specialist input
• Any significant psychiatric conditions
• Any other significant disease, disorder or finding, which, in the opinion of a medically qualified Clinical Investigator, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer's ability to participate in the study
• Unlikely to comply with the study protocol
• Involved in current or recent research within the past 3 months (as judged by study investigators) *This refers to regions where Leishmania major-transmitting sand flies are endemic including (but not limited to) the Middle East, Sub-Saharan Africa, and Asia.