<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03813069</url>
  </required_header>
  <id_info>
    <org_study_id>2018-kep-132</org_study_id>
    <nct_id>NCT03813069</nct_id>
  </id_info>
  <brief_title>Testing Insect Repellents Against Musca Sorbens, the Vector of Trachoma</brief_title>
  <official_title>A Within-subject Laboratory and Field Trial to Test the Use of Commercially Available Insect Repellents Against Contact From Musca Sorbens, the Putative Vector of Trachoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>London School of Hygiene and Tropical Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Federal Minstry of Health of Ethiopia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oromia Regional Health Bureau, Ethiopia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Fred Hollows Foundation, Ethiopia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Fred Hollows Foundation, UK</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Fred Hollows Foundation, Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>London School of Hygiene and Tropical Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Musca sorbens, a fly that feeds from ocular and nasal discharge on humans, is thought to be&#xD;
      the vector of trachoma. We are developing methods of fly control that specifically target&#xD;
      this species, in the hope of interrupting Ct transmission. To our knowledge, the use of&#xD;
      commercially available insect repellents has never been tested for prevention of Musca&#xD;
      sorbens fly-eye contact (i.e. nuisance and landing in the peri-ocular area). Given the likely&#xD;
      necessity for prolonged and/or high frequency fly-eye contact for Ct transmission, the&#xD;
      reduction of these contacts through the use of fly repellents presents an exciting&#xD;
      opportunity for disease control. Here we propose a within-subject, non-masked, trial of the&#xD;
      use of commercially available insect repellents against Musca sorbens, with two consecutive&#xD;
      participant groups in the laboratory and in the field, and a primary endpoint of measuring&#xD;
      the protective efficacy of each repellent product. Repellent products will be chosen from:&#xD;
      DEET (N,N-diethyl-3-methylbenzamide), IR3535 (3-[N-butyl-N-acetyl]-aminopropionic acid ethyl&#xD;
      ester), Picaridin (2-(2-hydroxyethyl)-1-piperidinecarboxylic acid 1-methylpropyl ester); PMD&#xD;
      (para-Menthane-3,8-diol) or permethrin&#xD;
      (m-Phenoxybenzyl)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate).&#xD;
      Products tested will be either (1) topical repellents, or (2) in long-lasting, plastic&#xD;
      formulations of repellents that can be worn on the body (wearable repellent technologies).&#xD;
      The insect repellent synergist Vanillin (4-Hydroxy-3-methoxybenzaldehyde) may be added to the&#xD;
      long-lasting plastic formulations, to improve the duration of protection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction&#xD;
&#xD;
      Trachoma&#xD;
&#xD;
      Trachoma, a Neglected Tropical Disease (NTD), is the commonest infectious cause of blindness&#xD;
      globally, affecting some of the world's poorest communities. Trachoma is caused by repeated&#xD;
      ocular infection with the bacterium Chlamydia trachomatis (Ct). Active trachoma begins in&#xD;
      childhood with recurrent episodes of follicular conjunctivitis (TF). Chronic inflammation&#xD;
      results in immunologically mediated conjunctival scarring and in-turned eyelashes scratching&#xD;
      the eye: trichiasis. Eventually sight is lost from irreversible corneal opacification.&#xD;
&#xD;
      Trachoma is currently endemic in 42 countries. The latest estimates from the Global Trachoma&#xD;
      Mapping Programme (GTMP) suggest that 180 million people live in trachoma endemic areas and&#xD;
      3.2 million people have trachomatous trichiasis. Around 2.2 million people are visually&#xD;
      impaired, of whom 1.2 million are blind. More than 80% of the burden of active trachoma is&#xD;
      concentrated in 14 countries, mainly in the Sahel of West Africa and savannahs of East and&#xD;
      Central Africa, where water supplies are often scarce.&#xD;
&#xD;
      Trachoma in Ethiopia&#xD;
&#xD;
      Ethiopia is working towards eliminating trachoma by 2020 and began implementing the SAFE&#xD;
      strategy as part of national policy in 2003. This has focused on the provision of improved&#xD;
      trichiasis surgery, mass drug administration (MDA) and the distribution of public health&#xD;
      messages by radio, video, and printed material. From 2001-2015 more than one million&#xD;
      trichiasis surgeries were performed, over 170 million doses of azithromycin were given&#xD;
      through MDA and more than 24 million latrines were built. Despite these encouraging efforts,&#xD;
      trachoma remains a public health problem in many regions of the country, and the burden of&#xD;
      disease is far above the elimination targets set by the World Health Organisation (WHO). In&#xD;
      many of these communities, despite seven years of annual or biannual high-coverage MDA, the&#xD;
      prevalence of TF remains well above threshold for continuing MDA. Data on Ct prevalence after&#xD;
      repeated rounds of MDA in hyperendemic settings such as Ethiopia, indicate that reliable&#xD;
      long-term control is not consistently achieved, with gradual re-emergence of infection being&#xD;
      typical.&#xD;
&#xD;
      Flies and Trachoma&#xD;
&#xD;
      Flies are likely to contribute to Ct transmission in some locations. The three members of the&#xD;
      species complex Musca sorbens live in close association with humans across the Old World&#xD;
      tropics and sub-tropics, Asia, the Pacific Islands and Australasian regions. The African&#xD;
      species, M. sorbens and Musca biseta, are collectively known as The Bazaar fly, but all are&#xD;
      also known as 'face flies', because of their habit of aggressively visiting the face to&#xD;
      obtain the protein and liquid found in ocular and nasal secretions. When M. sorbens flies&#xD;
      visit the face to feed, they can pick up Ct and transfer it on their bodies to another&#xD;
      person. This is called mechanical transmission. Sometimes the house fly, Musca domestica,&#xD;
      will also display eye-seeking behaviour, but across most trachoma-endemic regions, the vast&#xD;
      majority of fly-eye contacts are made by M. sorbens. As well as transmitting trachoma, M.&#xD;
      sorbens has been found to harbour enteric pathogens. In communities without adequate&#xD;
      sanitation such as pit latrines, filth flies including M. sorbens have direct access to&#xD;
      faecal breeding sites in the form of open defection. Here, they contact diarrhoea-causing&#xD;
      pathogens, and subsequent contact to children's faces, or contamination of eating surfaces,&#xD;
      can lead to pathogen transmission.&#xD;
&#xD;
      Ct can be cultured from guts and limbs of M. domestica fed on Ct-infected egg yolk. Using a&#xD;
      tightly controlled guinea pig trachoma model, Chlamydia psittaci was transmitted by flies&#xD;
      from infected to uninfected eyes. Infection was established consistently if the time between&#xD;
      flies feeding on infected guinea pig ocular secretions and being exposed to uninfected guinea&#xD;
      pigs was under one hour. Other, circumstantial, evidence suggests that flies contribute to&#xD;
      the transmission of trachoma. In randomised controlled trials, significantly decreasing the&#xD;
      M. sorbens population through long-term insecticide spraying led to decreases in the&#xD;
      prevalence of clinical signs of active trachoma (infection not tested). However, azithromycin&#xD;
      MDA combined with intensive insecticide spraying in other regions had no effect. Multiple&#xD;
      transmission routes complicate trachoma epidemiology, and the extent to which flies&#xD;
      contribute to transmission must also be dependent on local factors such as fly seasonality,&#xD;
      abundance and local environmental factors that influence fly population dynamics. Two studies&#xD;
      tested M. sorbens caught leaving faces of Ethiopian children for Ct by polymerase chain&#xD;
      reaction (PCR); 15-23% of flies were positive. In The Gambia, Ct positive flies were also&#xD;
      caught from children's faces. These data strongly suggest M. sorbens is a vector of trachoma,&#xD;
      however, its relative importance probably varies by setting. Although it is probable that&#xD;
      flies are involved in transmission, this pathway is poorly understood.&#xD;
&#xD;
      Olfactory cues have been exploited for monitoring and control of vector populations for many&#xD;
      years, through the deployment of odour-baited traps. However, in recent years the use of such&#xD;
      traps for population suppression of disease vectors has received increased attention, and&#xD;
      recently the potential of these methods for malaria control was empirically demonstrated for&#xD;
      the first time. One of the most long-standing and established examples of the use of&#xD;
      odour-baited traps is the control of tsetse flies and Human African Trypanosomiasis in East&#xD;
      Africa.&#xD;
&#xD;
      The investigators have recently conducted field studies in Oromia, Ethiopia, during Phase 1&#xD;
      and Phase 2 of the Stronger SAFE programme, designing a trap from locally sourced and cheaply&#xD;
      available materials. The performance of this trap was tested, baited with a commercial lure,&#xD;
      relative to several other commercially available fly traps and found to be superior. A major&#xD;
      advantage of odour-baited trapping for fly control is that it is not associated with&#xD;
      environmental impact concerns. This is in contrast to widespread insecticide spraying, which&#xD;
      although has been shown to suppress fly populations very successfully, can be damaging to the&#xD;
      environment.&#xD;
&#xD;
      Insect repellents are used world-wide to prevent nuisance biting by non-vector species, and&#xD;
      to prevent disease transmission by vectors in disease-endemic regions. Although the use of&#xD;
      plants with repellent qualities, either by burning leaves or presenting fresh foliage, is&#xD;
      prevalent in many regions, commercially available topical repellents are rarely used by&#xD;
      people in low-income and disease-endemic countries. This is because of cost, availability,&#xD;
      and the impracticality of a product that requires repeat application. However, when use of&#xD;
      insect repellents has been successfully adopted by communities, they have been found to be&#xD;
      protective against malaria. Repellents have also been successfully used to control other&#xD;
      arthropods of public health significance, including lice and the chigoe flea. A recent review&#xD;
      of the evidence that topical insect repellents can be used to protect against clinical&#xD;
      malaria or malaria infection found insufficient evidence, and called for better designed&#xD;
      trials to generate higher-certainty evidence.&#xD;
&#xD;
      There is growing interest in the use of repellents as personal protection from disease&#xD;
      transmission, particularly around the use of insecticide-treated clothing, which can repel&#xD;
      biting insects. In these instances, the insecticide used has spatially repellent properties&#xD;
      or is a contact irritant, which protects the individual user and the insecticides are not&#xD;
      sprayed into the environment. Insecticide-treated clothing has been shown to provide&#xD;
      protection from both malaria and leishmaniasis. Another study looked at the use of&#xD;
      permethrin-treated headscarves for Afghan women in a Pakistani refugee camp, and found a&#xD;
      reduction in the incidence of malaria in people under 20 years old. There is better evidence&#xD;
      for the use of insecticide-treated clothing against malaria transmission, particularly&#xD;
      advocated in areas where more evidence-based vector control strategies such as long-lasting&#xD;
      insecticide-treated bed nets are not appropriate. Again, however, further high-quality&#xD;
      studies are required to improve the efficacy evidence base.&#xD;
&#xD;
      Using the M. sorbens colony that the investigators have established at LSHTM, preliminary&#xD;
      studies have been conducted that demonstrate M. sorbens are susceptible to most commercially&#xD;
      available repellents. The investigators have found evidence that the insecticide permethrin&#xD;
      has some spatial repellency to M. sorbens, if impregnated at safe doses into fabric scarves.&#xD;
      In areas of high fly density, it is expected that the nuisance caused by these flies may&#xD;
      allow such an intervention to be successful, as the immediate benefit of reduced face contact&#xD;
      would encourage continued uptake of this intervention. Attractant (odour-baited trap) and&#xD;
      repellent (commercially available repellents) technologies will be combined to create a&#xD;
      &quot;push-pull&quot; strategy to reduce vector-host contact and attract flies to lethal odour-baited&#xD;
      traps that will supress populations.&#xD;
&#xD;
      Research hypothesis&#xD;
&#xD;
      Commercially available insect repellent products can be used to decrease contact to the face,&#xD;
      particularly the eyes, nose and mouth, by the eye-seeking fly Musca sorbens. The protection&#xD;
      afforded by insect repellents will prevent transmission of Chlamydia trachomatis by infected&#xD;
      flies, as well as reducing the nuisance caused by this species.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 10, 2019</start_date>
  <completion_date type="Actual">December 23, 2019</completion_date>
  <primary_completion_date type="Actual">December 23, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a within-subject, non-masked, trial of the use of commercially available insect repellents against Musca sorbens, with two consecutive participant groups in the laboratory and in the field, and a primary endpoint of measuring the protective efficacy of each repellent product.&#xD;
The first (laboratory-based) study has one arm, in which all participants test all repellent products. Those that are found to generate at least 30 % protective efficacy will be tested in the second (field-based) study, which will have four arms. Up to three arms will test a repellent product and there will be a control arm.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Protective Efficacy (PE)</measure>
    <time_frame>2 months</time_frame>
    <description>The protection (protective efficacy, p) afforded by a repellent product will be presented as a percentage. p will be estimated by comparing fly-arm contact duration and fly-eye contact frequency, in laboratory and field trials respectively, after application (or wearing) of the repellent product to that during the control period.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Complete Protection Time (CPT)</measure>
    <time_frame>3 months</time_frame>
    <description>Median CPT will be estimated in stage two ('persistence') laboratory trials only, for those repellents that demonstrated more than 30 % PE. The complete protection time for a specific dose will be estimated as the time elapsed until the first fly landing on the arm in each replicate, and based on repeat estimates of CPT, the mCPT will be estimated using a Kaplan-Meier function.</description>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">64</enrollment>
  <condition>Trachoma</condition>
  <arm_group>
    <arm_group_label>Laboratory study</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Field study: IR3535</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Field study: Permethrin lower dose</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Field study: Permethrin higher dose</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Field study: control arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>IR3535</intervention_name>
    <description>The topical repellent IR3535 (3-[N-butyl-N-acetyl]-aminopropionic acid ethyl ester) only</description>
    <arm_group_label>Field study: IR3535</arm_group_label>
    <arm_group_label>Laboratory study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Permethrin lower dose</intervention_name>
    <description>A fabric scarf, impregnated with the insecticide permethrin (m-Phenoxybenzyl)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate) that has contact irritancy/spatial repellency. Dose appropriate to children of 10-20 kg.</description>
    <arm_group_label>Field study: Permethrin lower dose</arm_group_label>
    <arm_group_label>Laboratory study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Permethrin higher dose</intervention_name>
    <description>A fabric scarf, impregnated with the insecticide permethrin (m-Phenoxybenzyl)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate) that has contact irritancy/spatial repellency. Dose appropriate to children more than 20 kg.</description>
    <arm_group_label>Field study: Permethrin higher dose</arm_group_label>
    <arm_group_label>Laboratory study</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Laboratory trial eligibility criteria&#xD;
&#xD;
          1. Participant is aged &gt; 18 years and &lt; 65 years and in good health&#xD;
&#xD;
          2. Participant has a good understanding of the procedures of the study and agrees to&#xD;
             abide to these procedures&#xD;
&#xD;
          3. Participant is able to communicate well with the investigator, and attend the&#xD;
             laboratory for all aspects of the laboratory studies&#xD;
&#xD;
          4. Participant has no known adverse reactions, or evidence at screening of adverse&#xD;
             reactions, to the commercially available repellents DEET, PMD, IR3535, Picaridin or&#xD;
             Permethrin, or to Vanilla&#xD;
&#xD;
          5. Participant has no known history of skin allergies or hypersensitivity to topical&#xD;
             creams&#xD;
&#xD;
          6. Participant agrees to a pre-trial skin reactivity test for all the repellents that&#xD;
             will be used in the trial&#xD;
&#xD;
          7. If in the event of the participant experiencing an adverse reaction to a repellent&#xD;
             during the trial, the participant agrees to inform his/her general practitioner and&#xD;
             seek appropriate treatment if necessary&#xD;
&#xD;
          8. Participant is willing to allow laboratory-reared Musca sorbens flies to land and&#xD;
             crawl on their arm, during the modified arm-in-cage assay, for periods of up to ten&#xD;
             minutes at a time&#xD;
&#xD;
          9. Participant agrees not to use any perfumed or scented product, including bathing&#xD;
             products, for a 24-hour period before each laboratory session&#xD;
&#xD;
         10. Participant has signed informed consent&#xD;
&#xD;
         11. Participant is not a smoker, and will agree to refraining from smoking for the 12&#xD;
             hours before each laboratory trial&#xD;
&#xD;
        Field trial eligibility criteria&#xD;
&#xD;
          1. Participant lives in the designated study site&#xD;
&#xD;
          2. Participating households must be within a one-hour drive of Feya General Hospital&#xD;
&#xD;
          3. Participant considers themselves to be in good health, as does the parent or guardian&#xD;
&#xD;
          4. Participant is aged &gt; 3 years and &lt; 12 years&#xD;
&#xD;
          5. Participant has a good understanding of the procedures of the study and agrees to&#xD;
             abide to these procedures&#xD;
&#xD;
          6. The parent or guardian of the participant has a good understanding of the procedures&#xD;
             of the study and agrees to abide to these procedures&#xD;
&#xD;
          7. Participant is able to communicate well with the investigator or fieldworker who is&#xD;
             conducting the study&#xD;
&#xD;
          8. Participant has no known adverse reactions to the commercially available repellents&#xD;
             DEET, PMD, IR3535, Picaridin or Permethrin, or to Vanilla&#xD;
&#xD;
          9. Participant has no known history of skin allergies or hypersensitivity to topical&#xD;
             creams&#xD;
&#xD;
         10. Participant agrees to a pre-trial skin reactivity test for all the repellents that&#xD;
             will be used in the trial&#xD;
&#xD;
         11. If in the event of the participant experiencing an adverse reaction to a repellent&#xD;
             during the trial, the participant can request medical advice from the Stronger-SAFE&#xD;
             field team nurses if they wish&#xD;
&#xD;
         12. Participant is willing to sit still on a chair outside their house, for sequential&#xD;
             periods of up to ten minutes, allowing wild fly contact and landing on the body and&#xD;
             face, as much as possible without disturbing fly behaviour&#xD;
&#xD;
         13. Participant agrees not to use any perfumed or scented product, including bathing&#xD;
             products, for a 24-hour period before each laboratory session&#xD;
&#xD;
         14. Able and willing to give fully informed assent&#xD;
&#xD;
         15. The parent or guardian has signed informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Fred Hollows Foundation</name>
      <address>
        <city>Addis Ababa</city>
        <country>Ethiopia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London School of Hygiene and Tropical Medicine</name>
      <address>
        <city>London</city>
        <zip>WC1E 7HT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ethiopia</country>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Banks SD, Murray N, Wilder-Smith A, Logan JG. Insecticide-treated clothes for the control of vector-borne diseases: a review on effectiveness and safety. Med Vet Entomol. 2014 Aug;28 Suppl 1:14-25. doi: 10.1111/mve.12068. Epub 2014 Jun 10.</citation>
    <PMID>24912919</PMID>
  </reference>
  <reference>
    <citation>Bell, M.J. (2018) The impact of latrine construction on densities and pathogen infection rates of synanthropic flies and Culex quinquefasciatus mosquitoes in Odisha, India. PhD thesis.</citation>
  </reference>
  <reference>
    <citation>Burgess, I. (1993) The function of a repellent in head louse control. The Pharmaceutical Journal. 15, 674-675.</citation>
  </reference>
  <reference>
    <citation>Emerson PM, Bailey RL, Mahdi OS, Walraven GE, Lindsay SW. Transmission ecology of the fly Musca sorbens, a putative vector of trachoma. Trans R Soc Trop Med Hyg. 2000 Jan-Feb;94(1):28-32. doi: 10.1016/s0035-9203(00)90427-9.</citation>
    <PMID>10748893</PMID>
  </reference>
  <reference>
    <citation>Emerson PM, Bailey RL, Walraven GE, Lindsay SW. Human and other faeces as breeding media of the trachoma vector Musca sorbens. Med Vet Entomol. 2001 Sep;15(3):314-20. doi: 10.1046/j.0269-283x.2001.00318.x.</citation>
    <PMID>11583450</PMID>
  </reference>
  <reference>
    <citation>Emerson PM, Lindsay SW, Alexander N, Bah M, Dibba SM, Faal HB, Lowe KO, McAdam KP, Ratcliffe AA, Walraven GE, Bailey RL. Role of flies and provision of latrines in trachoma control: cluster-randomised controlled trial. Lancet. 2004 Apr 3;363(9415):1093-8. doi: 10.1016/S0140-6736(04)15891-1.</citation>
    <PMID>15064026</PMID>
  </reference>
  <reference>
    <citation>European Commission (2014) Assessment Report: Permethrin. Available at: http://dissemination.echa.europa.eu/Biocides/ActiveSubstances/1342-18/1342-18_Assessment_Report.pdf</citation>
  </reference>
  <reference>
    <citation>Faulde M, Uedelhoven W. A new clothing impregnation method for personal protection against ticks and biting insects. Int J Med Microbiol. 2006 May;296 Suppl 40:225-9. doi: 10.1016/j.ijmm.2006.01.008. Epub 2006 Mar 9.</citation>
    <PMID>16524779</PMID>
  </reference>
  <reference>
    <citation>Feldmeier H, Kehr JD, Heukelbach J. A plant-based repellent protects against Tunga penetrans infestation and sand flea disease. Acta Trop. 2006 Oct;99(2-3):126-36. doi: 10.1016/j.actatropica.2006.05.013. Epub 2006 Sep 29.</citation>
    <PMID>17010927</PMID>
  </reference>
  <reference>
    <citation>Forsey T, Darougar S. Transmission of chlamydiae by the housefly. Br J Ophthalmol. 1981 Feb;65(2):147-50. doi: 10.1136/bjo.65.2.147.</citation>
    <PMID>7459318</PMID>
  </reference>
  <reference>
    <citation>Heng S, Durnez L, Gryseels C, Van Roey K, Mean V, Uk S, Siv S, Grietens KP, Sochantha T, Coosemans M, Sluydts V. Assuring access to topical mosquito repellents within an intensive distribution scheme: a case study in a remote province of Cambodia. Malar J. 2015 Nov 24;14:468. doi: 10.1186/s12936-015-0960-4.</citation>
    <PMID>26597653</PMID>
  </reference>
  <reference>
    <citation>Hill N, Lenglet A, Arnez AM, Carneiro I. Plant based insect repellent and insecticide treated bed nets to protect against malaria in areas of early evening biting vectors: double blind randomised placebo controlled clinical trial in the Bolivian Amazon. BMJ. 2007 Nov 17;335(7628):1023. doi: 10.1136/bmj.39356.574641.55. Epub 2007 Oct 16.</citation>
    <PMID>17940319</PMID>
  </reference>
  <reference>
    <citation>Homan T, Hiscox A, Mweresa CK, Masiga D, Mukabana WR, Oria P, Maire N, Pasquale AD, Silkey M, Alaii J, Bousema T, Leeuwis C, Smith TA, Takken W. The effect of mass mosquito trapping on malaria transmission and disease burden (SolarMal): a stepped-wedge cluster-randomised trial. Lancet. 2016 Sep 17;388(10050):1193-201. doi: 10.1016/S0140-6736(16)30445-7. Epub 2016 Aug 9.</citation>
    <PMID>27520594</PMID>
  </reference>
  <reference>
    <citation>Lee S, Alemayehu W, Melese M, Lakew T, Lee D, Yi E, Cevallos V, Donnellan C, Zhou Z, Chidambaram JD, Gaynor BD, Whitcher JP, Lietman TM. Chlamydia on children and flies after mass antibiotic treatment for trachoma. Am J Trop Med Hyg. 2007 Jan;76(1):129-31.</citation>
    <PMID>17255240</PMID>
  </reference>
  <reference>
    <citation>Maia MF, Kliner M, Richardson M, Lengeler C, Moore SJ. Mosquito repellents for malaria prevention. Cochrane Database Syst Rev. 2018 Feb 6;2(2):CD011595. doi: 10.1002/14651858.CD011595.pub2.</citation>
    <PMID>29405263</PMID>
  </reference>
  <reference>
    <citation>Massue DJ, Moore SJ, Mageni ZD, Moore JD, Bradley J, Pigeon O, Maziba EJ, Mandike R, Kramer K, Kisinza WN, Overgaard HJ, Lorenz LM. Durability of Olyset campaign nets distributed between 2009 and 2011 in eight districts of Tanzania. Malar J. 2016 Mar 18;15:176. doi: 10.1186/s12936-016-1225-6.</citation>
    <PMID>26993981</PMID>
  </reference>
  <reference>
    <citation>Miller K, Pakpour N, Yi E, Melese M, Alemayehu W, Bird M, Schmidt G, Cevallos V, Olinger L, Chidambaram J, Gaynor B, Whitcher J, Lietman T. Pesky trachoma suspect finally caught. Br J Ophthalmol. 2004 Jun;88(6):750-1. doi: 10.1136/bjo.2003.038661.</citation>
    <PMID>15148205</PMID>
  </reference>
  <reference>
    <citation>Moore SJ, Hill N, Ruiz C, Cameron MM. Field evaluation of traditionally used plant-based insect repellents and fumigants against the malaria vector Anopheles darlingi in Riberalta, Bolivian Amazon. J Med Entomol. 2007 Jul;44(4):624-30. doi: 10.1603/0022-2585(2007)44[624:feotup]2.0.co;2.</citation>
    <PMID>17695017</PMID>
  </reference>
  <reference>
    <citation>Orsborne J, DeRaedt Banks S, Hendy A, Gezan SA, Kaur H, Wilder-Smith A, Lindsay SW, Logan JG. Personal Protection of Permethrin-Treated Clothing against Aedes aegypti, the Vector of Dengue and Zika Virus, in the Laboratory. PLoS One. 2016 May 17;11(5):e0152805. doi: 10.1371/journal.pone.0152805. eCollection 2016.</citation>
    <PMID>27187593</PMID>
  </reference>
  <reference>
    <citation>Paru R, Hii J, Lewis D, Alpers MP. Relative repellency of woodsmoke and topical applications of plant products against mosquitoes. P N G Med J. 1995 Sep;38(3):215-21.</citation>
    <PMID>9522861</PMID>
  </reference>
  <reference>
    <citation>Richards SL, Balanay JAG, Harris JW, Banks VM, Meshnick S. Residual Effectiveness of Permethrin-Treated Clothing for Prevention of Mosquito Bites Under Simulated Conditions. J Environ Health. 2017 Apr;79(8):8-15.</citation>
    <PMID>29148650</PMID>
  </reference>
  <reference>
    <citation>Rowland M, Durrani N, Hewitt S, Mohammed N, Bouma M, Carneiro I, Rozendaal J, Schapira A. Permethrin-treated chaddars and top-sheets: appropriate technology for protection against malaria in Afghanistan and other complex emergencies. Trans R Soc Trop Med Hyg. 1999 Sep-Oct;93(5):465-72. doi: 10.1016/s0035-9203(99)90341-3.</citation>
    <PMID>10696399</PMID>
  </reference>
  <reference>
    <citation>Schwalfenberg S, Witt LH, Kehr JD, Feldmeier H, Heukelbach J. Prevention of tungiasis using a biological repellent: a small case series. Ann Trop Med Parasitol. 2004 Jan;98(1):89-94. doi: 10.1179/000349804225003091. No abstract available.</citation>
    <PMID>15000736</PMID>
  </reference>
  <reference>
    <citation>Sholdt LL, Schreck CE, Mwangelwa MI, Nondo J, Siachinji VJ. Evaluations of permethrin-impregnated clothing and three topical repellent formulations of deet against tsetse flies in Zambia. Med Vet Entomol. 1989 Apr;3(2):153-8. doi: 10.1111/j.1365-2915.1989.tb00493.x.</citation>
    <PMID>2519659</PMID>
  </reference>
  <reference>
    <citation>Sluydts V, Durnez L, Heng S, Gryseels C, Canier L, Kim S, Van Roey K, Kerkhof K, Khim N, Mao S, Uk S, Sovannaroth S, Grietens KP, Sochantha T, Menard D, Coosemans M. Efficacy of topical mosquito repellent (picaridin) plus long-lasting insecticidal nets versus long-lasting insecticidal nets alone for control of malaria: a cluster randomised controlled trial. Lancet Infect Dis. 2016 Oct;16(10):1169-1177. doi: 10.1016/S1473-3099(16)30148-7. Epub 2016 Jun 29.</citation>
    <PMID>27371977</PMID>
  </reference>
  <reference>
    <citation>Soto J, Medina F, Dember N, Berman J. Efficacy of permethrin-impregnated uniforms in the prevention of malaria and leishmaniasis in Colombian soldiers. Clin Infect Dis. 1995 Sep;21(3):599-602. doi: 10.1093/clinids/21.3.599.</citation>
    <PMID>8527550</PMID>
  </reference>
  <reference>
    <citation>West SK, Emerson PM, Mkocha H, McHiwa W, Munoz B, Bailey R, Mabey D. Intensive insecticide spraying for fly control after mass antibiotic treatment for trachoma in a hyperendemic setting: a randomised trial. Lancet. 2006 Aug 12;368(9535):596-600. doi: 10.1016/S0140-6736(06)69203-9.</citation>
    <PMID>16905024</PMID>
  </reference>
  <reference>
    <citation>World Health Organization (2017) How to design vector control efficacy trials: Guidance on phase III vector control field trial design provided by the Vector Control Advisory Group.</citation>
  </reference>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>April 7, 2020</last_update_submitted>
  <last_update_submitted_qc>April 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trachoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Permethrin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Formal reports will be written for the Ethiopian Federal and Regional health authority and the Federal Ministry of Science and Technology (FMOST). Reports will also be prepared for the Wellcome Trust and The Fred Hollows Foundation (Ethiopia and UK).&#xD;
To ensure operational uptake of the findings of the studies, we intend to present these data at the annual National Trachoma Task Force and NTD Research Symposium (Ethiopia). Additionally, we will present this research at the annual Trachoma Scientific Informal Workshop prior to the WHO GET2020 Alliance meeting. Scientific results will be published in Open Access in peer-reviewed journals and presented at relevant international conferences.&#xD;
The Sensitisation/Community Liaison Team will disseminate the results of the study to the study community in community dialogues and radio broadcasts in conjunction with The Fred Hollows Foundation Ethiopia Communications Team.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/69/NCT03813069/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03813069
org study id: 2018-kep-132
nct id: NCT03813069
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Musca sorbens, a fly that feeds from ocular and nasal discharge on humans, is thought to be
      the vector of trachoma. We are developing methods of fly control that specifically target
      this species, in the hope of interrupting Ct transmission. To our knowledge, the use of
      commercially available insect repellents has never been tested for prevention of Musca
      sorbens fly-eye contact (i.e. nuisance and landing in the peri-ocular area). Given the likely
      necessity for prolonged and/or high frequency fly-eye contact for Ct transmission, the
      reduction of these contacts through the use of fly repellents presents an exciting
      opportunity for disease control. Here we propose a within-subject, non-masked, trial of the
      use of commercially available insect repellents against Musca sorbens, with two consecutive
      participant groups in the laboratory and in the field, and a primary endpoint of measuring
      the protective efficacy of each repellent product. Repellent products will be chosen from:
      DEET (N,N-diethyl-3-methylbenzamide), IR3535 (3-[N-butyl-N-acetyl]-aminopropionic acid ethyl
      ester), Picaridin (2-(2-hydroxyethyl)-1-piperidinecarboxylic acid 1-methylpropyl ester); PMD
      (para-Menthane-3,8-diol) or permethrin
      (m-Phenoxybenzyl)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate).
      Products tested will be either (1) topical repellents, or (2) in long-lasting, plastic
      formulations of repellents that can be worn on the body (wearable repellent technologies).
      The insect repellent synergist Vanillin (4-Hydroxy-3-methoxybenzaldehyde) may be added to the
      long-lasting plastic formulations, to improve the duration of protection.
Introduction

      Trachoma

      Trachoma, a Neglected Tropical Disease (NTD), is the commonest infectious cause of blindness
      globally, affecting some of the world's poorest communities. Trachoma is caused by repeated
      ocular infection with the bacterium Chlamydia trachomatis (Ct). Active trachoma begins in
      childhood with recurrent episodes of follicular conjunctivitis (TF). Chronic inflammation
      results in immunologically mediated conjunctival scarring and in-turned eyelashes scratching
      the eye: trichiasis. Eventually sight is lost from irreversible corneal opacification.

      Trachoma is currently endemic in 42 countries. The latest estimates from the Global Trachoma
      Mapping Programme (GTMP) suggest that 180 million people live in trachoma endemic areas and
      3.2 million people have trachomatous trichiasis. Around 2.2 million people are visually
      impaired, of whom 1.2 million are blind. More than 80% of the burden of active trachoma is
      concentrated in 14 countries, mainly in the Sahel of West Africa and savannahs of East and
      Central Africa, where water supplies are often scarce.

      Trachoma in Ethiopia

      Ethiopia is working towards eliminating trachoma by 2020 and began implementing the SAFE
      strategy as part of national policy in 2003. This has focused on the provision of improved
      trichiasis surgery, mass drug administration (MDA) and the distribution of public health
      messages by radio, video, and printed material. From 2001-2015 more than one million
      trichiasis surgeries were performed, over 170 million doses of azithromycin were given
      through MDA and more than 24 million latrines were built. Despite these encouraging efforts,
      trachoma remains a public health problem in many regions of the country, and the burden of
      disease is far above the elimination targets set by the World Health Organisation (WHO). In
      many of these communities, despite seven years of annual or biannual high-coverage MDA, the
      prevalence of TF remains well above threshold for continuing MDA. Data on Ct prevalence after
      repeated rounds of MDA in hyperendemic settings such as Ethiopia, indicate that reliable
      long-term control is not consistently achieved, with gradual re-emergence of infection being
      typical.

      Flies and Trachoma

      Flies are likely to contribute to Ct transmission in some locations. The three members of the
      species complex Musca sorbens live in close association with humans across the Old World
      tropics and sub-tropics, Asia, the Pacific Islands and Australasian regions. The African
      species, M. sorbens and Musca biseta, are collectively known as The Bazaar fly, but all are
      also known as 'face flies', because of their habit of aggressively visiting the face to
      obtain the protein and liquid found in ocular and nasal secretions. When M. sorbens flies
      visit the face to feed, they can pick up Ct and transfer it on their bodies to another
      person. This is called mechanical transmission. Sometimes the house fly, Musca domestica,
      will also display eye-seeking behaviour, but across most trachoma-endemic regions, the vast
      majority of fly-eye contacts are made by M. sorbens. As well as transmitting trachoma, M.
      sorbens has been found to harbour enteric pathogens. In communities without adequate
      sanitation such as pit latrines, filth flies including M. sorbens have direct access to
      faecal breeding sites in the form of open defection. Here, they contact diarrhoea-causing
      pathogens, and subsequent contact to children's faces, or contamination of eating surfaces,
      can lead to pathogen transmission.

      Ct can be cultured from guts and limbs of M. domestica fed on Ct-infected egg yolk. Using a
      tightly controlled guinea pig trachoma model, Chlamydia psittaci was transmitted by flies
      from infected to uninfected eyes. Infection was established consistently if the time between
      flies feeding on infected guinea pig ocular secretions and being exposed to uninfected guinea
      pigs was under one hour. Other, circumstantial, evidence suggests that flies contribute to
      the transmission of trachoma. In randomised controlled trials, significantly decreasing the
      M. sorbens population through long-term insecticide spraying led to decreases in the
      prevalence of clinical signs of active trachoma (infection not tested). However, azithromycin
      MDA combined with intensive insecticide spraying in other regions had no effect. Multiple
      transmission routes complicate trachoma epidemiology, and the extent to which flies
      contribute to transmission must also be dependent on local factors such as fly seasonality,
      abundance and local environmental factors that influence fly population dynamics. Two studies
      tested M. sorbens caught leaving faces of Ethiopian children for Ct by polymerase chain
      reaction (PCR); 15-23% of flies were positive. In The Gambia, Ct positive flies were also
      caught from children's faces. These data strongly suggest M. sorbens is a vector of trachoma,
      however, its relative importance probably varies by setting. Although it is probable that
      flies are involved in transmission, this pathway is poorly understood.

      Olfactory cues have been exploited for monitoring and control of vector populations for many
      years, through the deployment of odour-baited traps. However, in recent years the use of such
      traps for population suppression of disease vectors has received increased attention, and
      recently the potential of these methods for malaria control was empirically demonstrated for
      the first time. One of the most long-standing and established examples of the use of
      odour-baited traps is the control of tsetse flies and Human African Trypanosomiasis in East
      Africa.

      The investigators have recently conducted field studies in Oromia, Ethiopia, during Phase 1
      and Phase 2 of the Stronger SAFE programme, designing a trap from locally sourced and cheaply
      available materials. The performance of this trap was tested, baited with a commercial lure,
      relative to several other commercially available fly traps and found to be superior. A major
      advantage of odour-baited trapping for fly control is that it is not associated with
      environmental impact concerns. This is in contrast to widespread insecticide spraying, which
      although has been shown to suppress fly populations very successfully, can be damaging to the
      environment.

      Insect repellents are used world-wide to prevent nuisance biting by non-vector species, and
      to prevent disease transmission by vectors in disease-endemic regions. Although the use of
      plants with repellent qualities, either by burning leaves or presenting fresh foliage, is
      prevalent in many regions, commercially available topical repellents are rarely used by
      people in low-income and disease-endemic countries. This is because of cost, availability,
      and the impracticality of a product that requires repeat application. However, when use of
      insect repellents has been successfully adopted by communities, they have been found to be
      protective against malaria. Repellents have also been successfully used to control other
      arthropods of public health significance, including lice and the chigoe flea. A recent review
      of the evidence that topical insect repellents can be used to protect against clinical
      malaria or malaria infection found insufficient evidence, and called for better designed
      trials to generate higher-certainty evidence.

      There is growing interest in the use of repellents as personal protection from disease
      transmission, particularly around the use of insecticide-treated clothing, which can repel
      biting insects. In these instances, the insecticide used has spatially repellent properties
      or is a contact irritant, which protects the individual user and the insecticides are not
      sprayed into the environment. Insecticide-treated clothing has been shown to provide
      protection from both malaria and leishmaniasis. Another study looked at the use of
      permethrin-treated headscarves for Afghan women in a Pakistani refugee camp, and found a
      reduction in the incidence of malaria in people under 20 years old. There is better evidence
      for the use of insecticide-treated clothing against malaria transmission, particularly
      advocated in areas where more evidence-based vector control strategies such as long-lasting
      insecticide-treated bed nets are not appropriate. Again, however, further high-quality
      studies are required to improve the efficacy evidence base.

      Using the M. sorbens colony that the investigators have established at LSHTM, preliminary
      studies have been conducted that demonstrate M. sorbens are susceptible to most commercially
      available repellents. The investigators have found evidence that the insecticide permethrin
      has some spatial repellency to M. sorbens, if impregnated at safe doses into fabric scarves.
      In areas of high fly density, it is expected that the nuisance caused by these flies may
      allow such an intervention to be successful, as the immediate benefit of reduced face contact
      would encourage continued uptake of this intervention. Attractant (odour-baited trap) and
      repellent (commercially available repellents) technologies will be combined to create a
      "push-pull" strategy to reduce vector-host contact and attract flies to lethal odour-baited
      traps that will supress populations.

      Research hypothesis

      Commercially available insect repellent products can be used to decrease contact to the face,
      particularly the eyes, nose and mouth, by the eye-seeking fly Musca sorbens. The protection
      afforded by insect repellents will prevent transmission of Chlamydia trachomatis by infected
      flies, as well as reducing the nuisance caused by this species.
allocation: Randomized
intervention model: Single Group Assignment
intervention model description: This is a within-subject, non-masked, trial of the use of commercially available insect repellents against Musca sorbens, with two consecutive participant groups in the laboratory and in the field, and a primary endpoint of measuring the protective efficacy of each repellent product.
The first (laboratory-based) study has one arm, in which all participants test all repellent products. Those that are found to generate at least 30 % protective efficacy will be tested in the second (field-based) study, which will have four arms. Up to three arms will test a repellent product and there will be a control arm.
primary purpose: Prevention
masking: Single (Outcomes Assessor)
measure: Protective Efficacy (PE)
time frame: 2 months
description: The protection (protective efficacy, p) afforded by a repellent product will be presented as a percentage. p will be estimated by comparing fly-arm contact duration and fly-eye contact frequency, in laboratory and field trials respectively, after application (or wearing) of the repellent product to that during the control period.
measure: Complete Protection Time (CPT)
time frame: 3 months
description: Median CPT will be estimated in stage two ('persistence') laboratory trials only, for those repellents that demonstrated more than 30 % PE. The complete protection time for a specific dose will be estimated as the time elapsed until the first fly landing on the arm in each replicate, and based on repeat estimates of CPT, the mCPT will be estimated using a Kaplan-Meier function.
arm group label: Laboratory study
arm group type: Other
arm group label: Field study: IR3535
arm group type: Other
arm group label: Field study: Permethrin lower dose
arm group type: Other
arm group label: Field study: Permethrin higher dose
arm group type: Other
arm group label: Field study: control arm
arm group type: No Intervention
intervention type: Other
intervention name: IR3535
description: The topical repellent IR3535 (3-[N-butyl-N-acetyl]-aminopropionic acid ethyl ester) only
arm group label: Field study: IR3535
arm group label: Laboratory study
intervention type: Other
intervention name: Permethrin lower dose
description: A fabric scarf, impregnated with the insecticide permethrin (m-Phenoxybenzyl)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate) that has contact irritancy/spatial repellency. Dose appropriate to children of 10-20 kg.
arm group label: Field study: Permethrin lower dose
arm group label: Laboratory study
intervention type: Other
intervention name: Permethrin higher dose
description: A fabric scarf, impregnated with the insecticide permethrin (m-Phenoxybenzyl)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate) that has contact irritancy/spatial repellency. Dose appropriate to children more than 20 kg.
arm group label: Field study: Permethrin higher dose
arm group label: Laboratory study
criteria: 
gender: All
minimum age: 3 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
country: Ethiopia
country: United Kingdom
citation: Banks SD, Murray N, Wilder-Smith A, Logan JG. Insecticide-treated clothes for the control of vector-borne diseases: a review on effectiveness and safety. Med Vet Entomol. 2014 Aug;28 Suppl 1:14-25. doi: 10.1111/mve.12068. Epub 2014 Jun 10.
PMID: 24912919
citation: Bell, M.J. (2018) The impact of latrine construction on densities and pathogen infection rates of synanthropic flies and Culex quinquefasciatus mosquitoes in Odisha, India. PhD thesis.
citation: Burgess, I. (1993) The function of a repellent in head louse control. The Pharmaceutical Journal. 15, 674-675.
citation: Emerson PM, Bailey RL, Mahdi OS, Walraven GE, Lindsay SW. Transmission ecology of the fly Musca sorbens, a putative vector of trachoma. Trans R Soc Trop Med Hyg. 2000 Jan-Feb;94(1):28-32. doi: 10.1016/s0035-9203(00)90427-9.
PMID: 10748893
citation: Emerson PM, Bailey RL, Walraven GE, Lindsay SW. Human and other faeces as breeding media of the trachoma vector Musca sorbens. Med Vet Entomol. 2001 Sep;15(3):314-20. doi: 10.1046/j.0269-283x.2001.00318.x.
PMID: 11583450
citation: Emerson PM, Lindsay SW, Alexander N, Bah M, Dibba SM, Faal HB, Lowe KO, McAdam KP, Ratcliffe AA, Walraven GE, Bailey RL. Role of flies and provision of latrines in trachoma control: cluster-randomised controlled trial. Lancet. 2004 Apr 3;363(9415):1093-8. doi: 10.1016/S0140-6736(04)15891-1.
PMID: 15064026
citation: European Commission (2014) Assessment Report: Permethrin. Available at: http://dissemination.echa.europa.eu/Biocides/ActiveSubstances/1342-18/1342-18_Assessment_Report.pdf
citation: Faulde M, Uedelhoven W. A new clothing impregnation method for personal protection against ticks and biting insects. Int J Med Microbiol. 2006 May;296 Suppl 40:225-9. doi: 10.1016/j.ijmm.2006.01.008. Epub 2006 Mar 9.
PMID: 16524779
citation: Feldmeier H, Kehr JD, Heukelbach J. A plant-based repellent protects against Tunga penetrans infestation and sand flea disease. Acta Trop. 2006 Oct;99(2-3):126-36. doi: 10.1016/j.actatropica.2006.05.013. Epub 2006 Sep 29.
PMID: 17010927
citation: Forsey T, Darougar S. Transmission of chlamydiae by the housefly. Br J Ophthalmol. 1981 Feb;65(2):147-50. doi: 10.1136/bjo.65.2.147.
PMID: 7459318
citation: Heng S, Durnez L, Gryseels C, Van Roey K, Mean V, Uk S, Siv S, Grietens KP, Sochantha T, Coosemans M, Sluydts V. Assuring access to topical mosquito repellents within an intensive distribution scheme: a case study in a remote province of Cambodia. Malar J. 2015 Nov 24;14:468. doi: 10.1186/s12936-015-0960-4.
PMID: 26597653
citation: Hill N, Lenglet A, Arnez AM, Carneiro I. Plant based insect repellent and insecticide treated bed nets to protect against malaria in areas of early evening biting vectors: double blind randomised placebo controlled clinical trial in the Bolivian Amazon. BMJ. 2007 Nov 17;335(7628):1023. doi: 10.1136/bmj.39356.574641.55. Epub 2007 Oct 16.
PMID: 17940319
citation: Homan T, Hiscox A, Mweresa CK, Masiga D, Mukabana WR, Oria P, Maire N, Pasquale AD, Silkey M, Alaii J, Bousema T, Leeuwis C, Smith TA, Takken W. The effect of mass mosquito trapping on malaria transmission and disease burden (SolarMal): a stepped-wedge cluster-randomised trial. Lancet. 2016 Sep 17;388(10050):1193-201. doi: 10.1016/S0140-6736(16)30445-7. Epub 2016 Aug 9.
PMID: 27520594
citation: Lee S, Alemayehu W, Melese M, Lakew T, Lee D, Yi E, Cevallos V, Donnellan C, Zhou Z, Chidambaram JD, Gaynor BD, Whitcher JP, Lietman TM. Chlamydia on children and flies after mass antibiotic treatment for trachoma. Am J Trop Med Hyg. 2007 Jan;76(1):129-31.
PMID: 17255240
citation: Maia MF, Kliner M, Richardson M, Lengeler C, Moore SJ. Mosquito repellents for malaria prevention. Cochrane Database Syst Rev. 2018 Feb 6;2(2):CD011595. doi: 10.1002/14651858.CD011595.pub2.
PMID: 29405263
citation: Massue DJ, Moore SJ, Mageni ZD, Moore JD, Bradley J, Pigeon O, Maziba EJ, Mandike R, Kramer K, Kisinza WN, Overgaard HJ, Lorenz LM. Durability of Olyset campaign nets distributed between 2009 and 2011 in eight districts of Tanzania. Malar J. 2016 Mar 18;15:176. doi: 10.1186/s12936-016-1225-6.
PMID: 26993981
citation: Miller K, Pakpour N, Yi E, Melese M, Alemayehu W, Bird M, Schmidt G, Cevallos V, Olinger L, Chidambaram J, Gaynor B, Whitcher J, Lietman T. Pesky trachoma suspect finally caught. Br J Ophthalmol. 2004 Jun;88(6):750-1. doi: 10.1136/bjo.2003.038661.
PMID: 15148205
citation: Moore SJ, Hill N, Ruiz C, Cameron MM. Field evaluation of traditionally used plant-based insect repellents and fumigants against the malaria vector Anopheles darlingi in Riberalta, Bolivian Amazon. J Med Entomol. 2007 Jul;44(4):624-30. doi: 10.1603/0022-2585(2007)44[624:feotup]2.0.co;2.
PMID: 17695017
citation: Orsborne J, DeRaedt Banks S, Hendy A, Gezan SA, Kaur H, Wilder-Smith A, Lindsay SW, Logan JG. Personal Protection of Permethrin-Treated Clothing against Aedes aegypti, the Vector of Dengue and Zika Virus, in the Laboratory. PLoS One. 2016 May 17;11(5):e0152805. doi: 10.1371/journal.pone.0152805. eCollection 2016.
PMID: 27187593
citation: Paru R, Hii J, Lewis D, Alpers MP. Relative repellency of woodsmoke and topical applications of plant products against mosquitoes. P N G Med J. 1995 Sep;38(3):215-21.
PMID: 9522861
citation: Richards SL, Balanay JAG, Harris JW, Banks VM, Meshnick S. Residual Effectiveness of Permethrin-Treated Clothing for Prevention of Mosquito Bites Under Simulated Conditions. J Environ Health. 2017 Apr;79(8):8-15.
PMID: 29148650
citation: Rowland M, Durrani N, Hewitt S, Mohammed N, Bouma M, Carneiro I, Rozendaal J, Schapira A. Permethrin-treated chaddars and top-sheets: appropriate technology for protection against malaria in Afghanistan and other complex emergencies. Trans R Soc Trop Med Hyg. 1999 Sep-Oct;93(5):465-72. doi: 10.1016/s0035-9203(99)90341-3.
PMID: 10696399
citation: Schwalfenberg S, Witt LH, Kehr JD, Feldmeier H, Heukelbach J. Prevention of tungiasis using a biological repellent: a small case series. Ann Trop Med Parasitol. 2004 Jan;98(1):89-94. doi: 10.1179/000349804225003091. No abstract available.
PMID: 15000736
citation: Sholdt LL, Schreck CE, Mwangelwa MI, Nondo J, Siachinji VJ. Evaluations of permethrin-impregnated clothing and three topical repellent formulations of deet against tsetse flies in Zambia. Med Vet Entomol. 1989 Apr;3(2):153-8. doi: 10.1111/j.1365-2915.1989.tb00493.x.
PMID: 2519659
citation: Sluydts V, Durnez L, Heng S, Gryseels C, Canier L, Kim S, Van Roey K, Kerkhof K, Khim N, Mao S, Uk S, Sovannaroth S, Grietens KP, Sochantha T, Menard D, Coosemans M. Efficacy of topical mosquito repellent (picaridin) plus long-lasting insecticidal nets versus long-lasting insecticidal nets alone for control of malaria: a cluster randomised controlled trial. Lancet Infect Dis. 2016 Oct;16(10):1169-1177. doi: 10.1016/S1473-3099(16)30148-7. Epub 2016 Jun 29.
PMID: 27371977
citation: Soto J, Medina F, Dember N, Berman J. Efficacy of permethrin-impregnated uniforms in the prevention of malaria and leishmaniasis in Colombian soldiers. Clin Infect Dis. 1995 Sep;21(3):599-602. doi: 10.1093/clinids/21.3.599.
PMID: 8527550
citation: West SK, Emerson PM, Mkocha H, McHiwa W, Munoz B, Bailey R, Mabey D. Intensive insecticide spraying for fly control after mass antibiotic treatment for trachoma in a hyperendemic setting: a randomised trial. Lancet. 2006 Aug 12;368(9535):596-600. doi: 10.1016/S0140-6736(06)69203-9.
PMID: 16905024
citation: World Health Organization (2017) How to design vector control efficacy trials: Guidance on phase III vector control field trial design provided by the Vector Control Advisory Group.
responsible party type: Sponsor
mesh term: Trachoma
mesh term: Permethrin
sharing ipd: Yes
ipd description: Formal reports will be written for the Ethiopian Federal and Regional health authority and the Federal Ministry of Science and Technology (FMOST). Reports will also be prepared for the Wellcome Trust and The Fred Hollows Foundation (Ethiopia and UK).
To ensure operational uptake of the findings of the studies, we intend to present these data at the annual National Trachoma Task Force and NTD Research Symposium (Ethiopia). Additionally, we will present this research at the annual Trachoma Scientific Informal Workshop prior to the WHO GET2020 Alliance meeting. Scientific results will be published in Open Access in peer-reviewed journals and presented at relevant international conferences.
The Sensitisation/Community Liaison Team will disseminate the results of the study to the study community in community dialogues and radio broadcasts in conjunction with The Fred Hollows Foundation Ethiopia Communications Team.
provided document: 