Cas12-Typhoid

Background

Typhoid fever, collectively referred to as enteric fever, is a systemic infection caused by the Gram-negative bacteria Salmonella enterica serovar Typhi (S. Typhi) and Paratyphi (S. Paratyphi) which causes approximately 17.8 million cases and 75,000–208,000 deaths worldwide each year. Despite notable progress, typhoid fever remains a major cause of disability and death, with billions of people likely to be exposed to the pathogens. The emergence of multidrug-resistant S. Typhi strains and the development of the typhoid carrier state have further complicated the management of the disease. Rapid and accurate diagnosis of typhoid fever as well as identification of possible MDR genes within S. Typhi pathogens has proved to be major challenges in the effective management and treatment of the disease.

Project description and aim

Typhoid fever is treatable with antibiotics but the clinical signs and symptoms of the disease are non-specific, hence laborious tests are essential for accurate diagnosis and take up to 7 days. Also, despite the emergence of multidrug-resistance (MDR) in African S. Typhi strains, there is a severe lack of data on MDR in Cameroon. There is, therefore, a need for rapid and accurate diagnosis of typhoid fever and the identification of possible MDR genes within S. Typhi pathogens. The CAS-12 Typhoid project is a new and innovative research project aimed at developing a locally-manufacturable typhoid diagnostic in Cameroon.

MboaLab Biotech in collaboration with the Open Bioeconomy Lab based at the University of Cambridge and the University of Buea in Cameroon have recently been awarded funding from the Global Challenges Research Fund to develop a proof-of-principle DNA-based typhoid diagnostic using cutting-edge molecular techniques. This project will run from February to July 2020 and the developed tool will be locally manufactured in Cameroon, have a great specificity; capable of distinguishing typhoid fever from paratyphoid while maintaining a reagent cost of < $1 per reaction.

Activities

In order to carry out this project, the team intends to take advantage of the respective resources and strengths of each partner involved. While the partnership with the University of Cambridge and OBL will foster academic capacity building and expertise in protein purification, molecular diagnostics cell-free protein expression as well as CRISPR/Cas based techniques; MboaLab Biotech and Buea University have the knowledge of local stakeholders and healthcare system and expertise in infectious disease epidemiology and immunology, drug-resistance surveillance as well as molecular biology. In addition to experimental research, MboaLab and Buea University will lead an engagement exercise interviewing local stakeholders to understand the requirements for diagnosing typhoid and pathways to impact within the local health system. This will include the adoption and use of molecular diagnostics within local hospitals, local policies to build capacity in public and private diagnostics laboratories.

The novel form of partnership between MboaLab and the University of Buea at the core of this project, will also promote new modes of institutional collaboration and partnership in Cameroon and demonstrate the efficacy of community-based innovation hubs and academic institutions combining strengths to address sustainable development goals in resource-limited environments.

Outputs and impacts

In the immediate term, this pump-priming project will build capacity in Cameroon for the use of cutting-edge research and diagnostic platform technology based on Cas12, providing valuable research skills and an open door for future collaboration. In the longer term, a locally produced, effective, low-cost detection method for typhoid has the potential to improve clinical treatment of typhoid fever and avoid some of the >500 deaths per year in Cameroon and the 75,000–208,000 deaths worldwide.