Only Skin Deep: non-invasive detection of Onchocerca microfilariae in dermis using electromagnetic microwaves

Onchocerciasis is a vector-borne neglected tropical disease caused by the filarial nematode, Onchocerca volvulus. Onchocerciasis affects 20.9 million of the poorest in society, with 14.6 million cases of skin disease and 1.15 million with visual impairment (river blindness). Current treatment is reliant on annual or semi-annual mass drug administrations of ivermectin, which only targets the skin dwelling microfilarial (mf) stage of infection. Thus, ivermectin has to be given for 15-17 years with high population coverage to break transmission. New drugs are in preclinical and clinical phase I/II development for onchocerciasis with a target profile of killing and/or permanently sterilising adult O. volvulus, leading to long-term clearance of mf from the skin. However, no sensitive and specific point-of-care method of diagnosing Onchocerca skin mf is available. This is problematic for the large-scale evaluation of new drug cures and assessments of elimination. The current gold standard is ‘skin snipping’, an invasive and laborious direct diagnostic technique which lacks sensitivity.

This project aims to address the current lack of a point-of-care sensitive diagnostic for skin onchocerciasis via characterising the unique changes of electromagnetic (EM) microwave spectra by Onchocerca mf within dermal tissues. The long-term goal of the research will be the development of a wearable trans-dermal sensor to detect skin mf, as has been developed for the detection of blood glucose and lactate levels. This work builds upon a successful collaboration between LSTM and Liverpool John Moores University to develop an EM sensor to quantify specific insecticide levels on household walls.  A research and development project, sponsored by The Bill and Melinda Gates Foundation, has been initiated for the human blood-dwelling mf, Brugia malayi, allowing for cross-comparison of changes to EM spectra by these two similar but unique filarial mf.

The student will experiment with mf in liquid culture and subsequently human explant dermis and/or 3D dermal organoids to determine whether skin infections can be achieved using Onchocerca mf, in collaboration with an industry partner, Alcyomics. In addition, a murine model of skin mf infection pre-established at our institute, can be used as an alternative source of parasitized dermis for EM wave characterisation within inflamed skin.

Where does the project lie on the Translational Pathway?

T1 (Basic Research)

Expected Outputs

The primary output is to determine the unique EM wave spectra of Onchocerca mf, determine the sensitivity of the signal within liquid culture or within dermis and determine whether the signal is sufficiently unique from related blood-borne mf.

Additional outputs will be the establishment of an in vitro dermal infection model of onchocerciasis for onward applications such as long-term dermal parasite cultures and propagations, intra-dermal drug pharmacokinetic / pharmacodynamics measurements and pathophysiology of onchodermatitis via interactions with immune cells.

Early characterisations of Onchocerca EM wave spectra and dermal mf in vitro infection models will be published by time of project completion.

The data will be used for competitive grant applications to manufacture a printed sensor for onward validations in the in vivo mf infection model and clinical proof-of-concept.

 

Training Opportunities

The student will benefit from training in whole animal physiology techniques (including acquiring regulatory licence and animal handling / animal procedures training) at LSTM and University of Liverpool Biological Services unit.

Further the student will benefit from an active collaboration with The Built Environment and Sustainable Technologies (BEST) Research Institute at LJMU.  BEST has an international reputation in the use of radio frequency and microwave technologies. The institute has state-of-the-art equipment and facilities with a specific focus on development of electromagnetic sensing systems including for health sector applications.

Skills Required

As the project is multidisciplinary in nature, this would suit a talented biologist with interests and experience in infection biology and /or cell biology or alternatively a student with an electrical engineering background who wishes to specialise in bioscience applications.

 

Key Publications associated with this project

Kot P, Muradov M, Ryecroft S, Ortoneda Pedrola M, Shaw A, Hemingway J, Deb R, Coleman M. 2018. Identification of Optimal Frequencies to Determine Alpha-Cypermethrin using Machine Learning Feature Selection Techniques IEEE Congress on Evolutionary Computation (IEEE CEC 2018) :1-7 DOI Author Url Public Url

Mason, A., Shaw. A, A. Al-Shamma’a

A Co-Planar Microwave Sensor for Biomedical Applications

https://doi.org/10.1016/j.proeng.2012.09.178

Korostynska, O., Mason, A., Al-Shamma’a, A.I (2014) 

Microwave sensors for the non-invasive monitoring of industrial and medical applications.

Sensor Review, 34(2): 182-191

 

Folkard SG, Taylor MJ, Butcher GA, Bianco AE

Protective responses against skin-dwelling microfilariae of Onchocerca lienalis in severe combined immunodeficient mice

Infection and Immunity 1997 Jul;65(7):2846-51.

DOI: 10.1128/IAI.65.7.2846-2851.1997

 

Halliday A, Guimaraes AF, Tyrer HE, Metuge HM, Patrick CN, Arnaud KO, Kwenti TD, Forsbrook G, Steven A, Cook D, Enyong P, Wanji S, Taylor MJ, Turner JD.

A murine macrofilaricide pre-clinical screening model for onchocerciasis and lymphatic filariasis.

Parasites and Vectors. 2014 Oct 24;7:472. doi: 10.1186/s13071-014-0472-z.

 

Deadline: Thursday 11th February 2021; 12:00 noon GMT

Further details on the MRC/DTP and CASE programmes and application guidance and process can be found here