Replacing the skin snip: Development and validation of a new rapid diagnostic test for river blindness

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 mass drug administrations (MDA) of ivermectin, which only targets the skin-dwelling microfilarial stage of infection. Thus, ivermectin must be given for at least 15 years with high population coverage to break transmission. New onchocerciasis drug cures are in clinical development which may in future be implemented as an alternative test-and-treat strategy to accelerate elimination.  The current gold standard diagnostic is ‘skin snipping’, an invasive and time-consuming laboratory diagnostic which lacks sensitivity and is poorly accepted by endemic communities. No sensitive and specific point-of-care method of diagnosing Onchocerca is available. This is problematic for widespread epidemiological mapping surveys, assessments of when to stop ivermectin administration, testing for infection before treating with alternative treatments, future evaluation of curative drug implementation and post MDA surveillance. The World Health Organisation has highlighted that a new diagnostic for onchocerciasis is a priority to achieve elimination targets by 2030.

In this project you will work with the industry partner, Mologic, to validate a new point-of-care rapid diagnostic serological test (Ov16 IgG4 antibody detection). Project activities will include: evaluation of diagnostic sensitivity and cross-reactivity with antibodies produced against closely related filarial infections (to assess specificity). For this you will plan validations utilising specimen collections held at LSTM. Further assay development may be required to remove cross-reactive antibodies by introduction of ‘decoy’ epitopes into the test and/or addition of distinct O. volvulus antigen epitopes to improve specificity. To improve evaluations, you will also collect new serum samples from uninfected endemic controls, mono-infected onchocerciasis patients as well as patients with mono-infections of related filarial infections (loiasis, mansonellosis) and verify infection status by immunological and molecular detection of parasite-specific filarial antigens. A final objective will be to evaluate time to sero-reversion following treatments with drug cures, including longitudinal serum samples currently being collected by Drugs for Neglected Diseases initiative as part of phase II clinical trials to evaluate efficacy of candidate cures and sample collections from a test-and-treat with doxycycline implementation trial (CouNTDown Consortium).

Where does the project lie on the Translational Pathway?

T1 – Basic Research, T2 – Human/Clinical Research

Expected Outputs

Advancement of a new point-of-care diagnostic for onchocerciasis to TRL4 (laboratory validation complete)

Publication of test development and validation in a leading biomedical journal

Data package to underpin future funding support via for instance BMGF, FCDO, Innovate-UK, USAID, MRC for widescale field validations.

Training Opportunities

Lab skills – PCR, immune-assay

bioinformatics

biostatistics

field work experience

Skills Required

Some general biomolecular and immunological experience would be desirable

The project would suit a highly self-motivated and independent student with excellent inter-personal skills to work within multiple laboratory and field settings.

Key Publications associated with this project

Johnston KL, Hong WD, Turner JD, O'Neill PM, Ward SA, Taylor MJ. Anti-Wolbachia drugs for filariasis. Trends Parasitol. 2021 Jul 3;. doi: 10.1016/j.pt.2021.06.004. [Epub ahead of print] Review. PubMed PMID: 34229954.

Forrer A, Wanji S, Obie ED, Nji TM, Hamill L, Ozano K, Piotrowski H, Dean L, Njouendou AJ, Ekanya R, Ndongmo WPC, Fung EG, Nnamdi DB, Abong RA, Beng AA, Eyong ME, Ndzeshang BL, Nkimbeng DA, Teghen S, Suireng A, Ashu EE, Kah E, Murdoch MM, Thomson R, Theobald S, Enyong P, Turner JD, Taylor MJ. Why onchocerciasis transmission persists after 15 annual ivermectin mass drug administrations in South-West Cameroon. BMJ Glob Health. 2021 Jan;6(1). doi: 10.1136/bmjgh-2020-003248. PubMed PMID: 33431378; PubMed Central PMCID: PMC7802695.

Macfarlane CL, Quek S, Pionnier N, Turner JD, Wanji S, Wagstaff SC, Taylor MJ. The insufficiency of circulating miRNA and DNA as diagnostic tools or as biomarkers of treatment efficacy for Onchocerca volvulus. Sci Rep. 2020 Apr 21;10(1):6672. doi: 10.1038/s41598-020-63249-4. PubMed PMID: 32317658; PubMed Central PMCID: PMC7174290.

Wanji S, Nji TM, Hamill L, Dean L, Ozano K, Njouendou AJ, Abong RA, Obie ED, Amuam A, Ekanya R, Ndongmo WPC, Ndzeshang BL, Fung EG, Nnamdi DB, Nkimbeng DA, Teghen S, Kah E, Piotrowski H, Forrer A, Khan JAM, Woode ME, Niessen L, Watson V, Njoumemi Z, Murdoch ME, Thomson R, Theobald S, Enyong P, Turner JD, Taylor MJ. Implementation of test-and-treat with doxycycline and temephos ground larviciding as alternative strategies for accelerating onchocerciasis elimination in an area of loiasis co-endemicity: the COUNTDOWN consortium multi-disciplinary study protocol. Parasit Vectors. 2019 Dec 4;12(1):574. doi: 10.1186/s13071-019-3826-8. PubMed PMID: 31801631; PubMed Central PMCID: PMC6894124.

Turner JD, Tendongfor N, Esum M, Johnston KL, Langley RS, Ford L, Faragher B, Specht S, Mand S, Hoerauf A, Enyong P, Wanji S, Taylor MJ. Macrofilaricidal activity after doxycycline only treatment of Onchocerca volvulus in an area of Loa loa co-endemicity: a randomized controlled trial. PLoS Negl Trop Dis. 2010 Apr 13;4(4):e660. doi: 10.1371/journal.pntd.0000660. PubMed PMID: 20405054; PubMed Central PMCID: PMC2854122.

Now Accepting Applications 

CLOSING DATE FOR APPLICATIONS: Application Portal closes: Wednesday 9th February 2022 (12:00 noon UK time)

Shortlisting complete by: End Feb/early March 2022

Interviews by: Late March/early April 2022

For more information on Eligibility, funding and how to apply please visit the MRC DTP/CASE pages