PATHFINDER

The challenge

Diagnosis is fundamental to medical care, but diagnosis of infectious diseases can be highly challenging. Many infections share similar symptoms, such as fever, and testing for a wide range of pathogens individually is inefficient and not necessarily reliable – an organism detected might not be the main cause of symptoms, or a causative agent might be missed if not present at the sampling site.

As a result, in many settings, there is a high rate of misdiagnosis or use of non-specific syndromic treatment. This means that patients do not necessarily receive the best treatment, and antibiotics are being used when not needed, driving the development of antimicrobial resistance (AMR). 

An alternative diagnostic strategy is to focus on the person (host) rather than the pathogen. It is now clear that host responses to different types of pathogens vary significantly. In particular, differences in gene activity can provide a signature of the type of infection (for example, whether it is bacterial, viral or malaria) and even identify specific pathogens. 

However, detecting the host response currently relies on sophisticated laboratory analyses. For it to deliver practical benefits, it needs to be packaged into devices that provide affordable, practical solutions suitable for low-resource settings.

The project

The PATHFINDER project is building on ground-breaking research into host gene activity signatures associated with infection, combined with innovative ‘lab-on-chip’ technology that enables sophisticated molecular analyses to be performed in compact devices suitable for use in routine healthcare settings.

Focusing on fever in children, the project is developing an easy-to-use point-of-care device that will generate key diagnostic information from a single blood sample. The results of its analysis will provide the probability that a patient has a bacterial or viral infection, as well as the likelihood of TB or malaria infections.

The project is based on a two-step process. First, RNA transcripts are extracted from blood samples using the SmartLid system. This requires no laboratory equipment or specialist skills and has already been successfully used in rural village settings in Burkina Faso and The Gambia.

The outputs from the RNA processing step are then analysed by a Lacewing lab-on-chip device. This channels the sample into ten microfluidic chambers, each of which can be analysed separately to generate a wealth of information about gene activity levels. The information generated is analysed on the device to provide the user with the probabilities of different infection types, all within 20 minutes.

The PATHFINDER project is refining the assays, fine-tuning RNA extraction, and comparing the device's results with equivalent laboratory tests. ProtonDx, the developer of Lacewing, will incorporate input from key stakeholders, including healthcare workers and community members, into its design specifications.

A field evaluation will then be carried out in Burkina Faso and Ghana, in which results will be gathered for 1,000 children with fever, of varying ages. The results will be compared with those obtained from tests currently used clinically, as well as from a wide range of additional laboratory tests. A range of samples from patients with confirmed diagnoses will also be tested to assess diagnostic performance. 

The project team will also carry out extensive stakeholder engagement to identify a regulatory pathway to approval, approaches to ensure commercial sustainability, and an access plan for eventual production of the device in Africa. Extensive analyses of study data will provide an indication of its potential impact based on a range of implementation strategies, which will also provide insights into its likely cost-effectiveness.

Impact

The PATHFINDER project could have a profound impact on diagnostic practices in sub-Saharan Africa. It will:

• Provide field data on the ability of the new device to detect tuberculosis and malaria infections in children with fever, and to distinguish between viral and bacterial infections.
• Provide clinicians with information enabling the use of the most appropriate treatments.
• Reduce the inappropriate use of antimicrobials, lessening the pressures driving AMR.
• Generate real-time epidemiological information that can be automatically shared with health authorities. 

The new technology, which could potentially be consolidated into a simple ‘sample in, results out’ device, could deliver benefits to both patients, who receive more appropriate treatments, and health systems, by reducing unnecessary antibiotic use, accelerating patient recovery, and reducing AMR risks. Moreover, the technology is highly adaptable, enabling countries to leapfrog costly central laboratories by using a flexible point-of-care diagnostic platform.