Affordable near-patient diagnostics to distinguish infectious diseases in the Philippines (AND2ID in Ph)

Lead Research Organisation: University of Cambridge
Department Name: Chemical Engineering and Biotechnology

Abstract

Acute fever may be caused by a range of pathogens, but clinical symptoms may be too non-specific to differentiate the causative organism, so correct diagnosis requires pathogen-specific diagnostic tests. These diagnostics are too expensive for routine use in resource-limited settings. This means that many patients are treated empirically with broad spectrum antibiotics, which may be unecessary, toxic, and increase the risk of antimicrobial resistance. Conversely delayed diagnosis and treatment may lead to poor outcomes.

A barrier to low-cost diagnostics in the Philippines, arises from a value chain that spans the world, without Purchasing Power Parity (PPP). If we could use technologies that can be manufactured locally, using local resources, then we have the first step to providing affordable diagnostics in resource poor areas, and delivering a sustained improvement in healthcare, while also developing the local economy.

We have made an enzyme (BOON-enzyme) that can do these tests and can be produced almost anywhere without special facilities. We have made the enzyme pink, so that you can see that it has been produced and we have a way of making it stick to sand so that it is very stable. We are going to use one of these enzymes - BOON-Taq in polymerase chain reaction (PCR) - to perform a clinical study in patients with suspected dengue and leptospirosis at the University of Santo Tomas in Manila, to assess the impact of the use of diagnostics on the patient pathway and the disease burden. As a result of these trials we will design a diagnostic kit that can be taken out to rural clinics and we will undertake clinical trials in such a clinic. We will support the study by developing a healthcare economics model of the impact of diagnostics on the patient pathway.

Technical Summary

Infectious diseases are a major cause of morbidity and mortality in the Philippines. Patients may present with fever and a wide range of non-specific symptoms, which are difficult to diagnose without specialist laboratory tests. Dengue is a major public health problem in the Philippines, and is endemic in all regions of the country. Leptospirosis is also endemic and may be misdiagnosed as dengue due to similarity in early clinical manifestations. Current diagnostic tests that rely on culture of pathogens or detection of raised antibody titres can take days to weeks to provide actionable results, and are too slow to guide initial patient management. In the first week of infection, nucleic acid testing (NAT) is the most reliable method to identify the causative agent, but these are expensive and usually require well-resourced laboratories.
The aim of this project is to create innovative low cost diagnostics, using local resources and show whether reduction in cost of a diagnostic has an impact on the ability to target treatment (including antibiotics) and lessen the impact of febrile illness on the patient, society and the economy.
The project has three steams: (1) Technological Innovation, (2) Clinical study, (3) Economic modelling and will result in
- Laboratory evaluation of a new NAT reagent in UK and Philippines
- Clinical trial of of the new test in Philippines with impact analysis of the clinical pathway.
- Development of an affordable diagnostic NAT platform design with prototype production for trials in a rural clinical site in Philippines for dengue and leptospirosis.
- Cost-effectiveness analysis and healthcare economics model of diagnostic platforms.
- Impact analysis of diagnostics on patient pathway.

Planned Impact

Who will potentially benefit from this research?
Infectious diseases are a major cause of morbidity and mortality in the Philippines. The diagnosis of the causative agent is often limited by the lack of availability and/or the high cost of laboratory diagnostic tests. Patients are therefore at risk of being over-treated with unnecessary antibiotics (which can drive antimicrobial resistance) or under-treated (resulting in poor clinical outcome. The development of a high-tech low-cost diagnostic that is able to diagnose infections such as dengue and leptospirosis would represent a major advance in the field and may be generalizable to other infections / countries.

The following groups of people are likely to benefit from this research:
- Study participants / patients
- Medical practitioners
- Medical practitioners
- Study investigators
- The wider scientific community
- Public health officials and policy makers
- The commercial sector
- The wider health economy

How will we maximize the impact of this research?
We will seek to actively identify and engage all of the relevant stakeholders at various stages of the research project i.e. during study preparation and set-up, during the course of the research studies, and when we present and disseminate the research findings.

This project will establish new collaborations between a multi-disciplinary group of researchers at leading UK and Philippine institutions. The investigators involved in the research will acquire new knowledge and expertise in development, manufacture, evaluation of a new high-tech low-cost diagnostic and its performance in a low-income setting

The research will result in capacity building through training of Philippine scientists, and enable the translation of a cutting-edge technology into a developing country setting, to enable local investigation and management of infectious diseases. We will organize / provide training to the study investigators, drawing on the existing expertise and infrastructure available in Cambridge Public Health England and the University of Santo Tomas. This will occur via training workshops and personal supervision of research assistants / clinical researchers.

The results of the studies will be presented at national and international meetings and published in peer-reviewed journals. It will therefore benefit the scientific community both in the Philippines and beyond. We will also disseminate the findings via institutional press releases / websites, standard media outlets (websites, newspaper, television and radio interviews) and social media (e.g. Twitter).

The information gained from these studies will be used to infom local policies for the diagnosis and management of infectious diseases during the course of the project. We will engage with local clinicians and policy makers to develop appropriate policies and procedures for use in hospital and rural settings. These may also be applicable to other low- or middle-income countries that have similarly high rates of dengue and leptospirosis.

In terms of beneficiaries within the commercial private sector these are likely to include companies that currently manufacture commercially available rapid diagnostic tests. The challenge will be for them to reduce the costs of consumables and manufacture so that these platforms can be used in low- and middle-income settings.

Finally, the research training, laboratory skills and data analysis skills obtained during the project are potentially transferable to other sectors.

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