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Paper microarrays as comprehensive low-cost point of care diagnostics of paediatric infectious diseases in Uganda (PI-POC)

BACKGROUND Infectious diseases are the leading cause of illness in children. When managing bacterial infections it is important and often crucial that antibiotics are given without delay, however the spread of antibiotic resistance due to over-prescription of antibiotics is becoming a major global public health problem and a challenge for clinicians everywhere. Consequently, there is a great need for tools that help clinicians manage febrile children, particularly in resource-limited settings, so that treatments and antibiotic regimens may be guided. Infections of the central nervous system (CNS) are life-threatening and annually more than 1.2 million cases of bacterial meningitis occur worldwide. Many of these occur in Sub-Saharan African areas with little or no access to laboratory diagnostics and are therefore left undiagnosed and untreated, with fatal outcomes. There is therefore a great need for diagnostic methods that are applicable to low-income settings. OBJECTIVES Development and clinical evaluation of new rapid multiplexed microarray technologies that can be applied as Point-of-Care (POC) diagnostics of paediatric infections of the CNS, with a particular focus on low-income countries. METHODS Our partners at Science for Life Laboratory have through extensive research and development shown that paperbased microarray concepts might be applicable as rapid, affordable, durable, easy-to-use, reliable and highly multiplexed diagnostic methods suitable for POC analysis in low-income countries. Through the use of paperbased protein and DNA microarrays, various biofluids (blood, urine, cerebrospinal fluid, saliva, sputum and others.) can easily be analysed and semiquantitative measurements of different proteins and biomarkers can be presented within minutes. Levels of blood glucose or inflammatory markers such as CRP, concentrations of electrolytes or the presence of pathogens such as bacteria or viruses in biofluids, are examples of what could be visualised in a time- and resource efficient manner in a low-income setting. The project is a true translational research project where the Karolinska Institute team will work together with partners at Science for Life Laboratory and the Mbarara University of Science & Technology and Médecins Sans Frontières Epicentre. We will conduct clinical evaluation studies of these novel paperbased microarray concepts of POC. The studies will be conducted at Mbarara Hospital, in South-Western Uganda. PLANNED STUDIES A) Development and optimize performance of a) novel combined affinity proteomic assay and b) novel PCR/DNA microarray assay, both amenable for POC diagnostics of paediatric CNS infection in low- and middle-income countries. B) Evaluation of the new POC techniques by applying them on 273 previously collected samples from paediatric patients in Uganda with suspected CNS infections. C) Determining the diagnostic accuracy and study the clinical utility and usability of the new POC test on paediatric CNS infections in a prospective study on 300 children with suspected CNS infections in a hospital setting in South-Western Uganda. SIGNIFICANCE This project has the potential to significantly improve diagnostics and outcomes of various infectious diseases affecting children in low-income countries. Our highly multidisciplinary and international research team is dedicated to the continued development of the described multiplexed paper-based microarray concepts towards the deployment of a POC tool that tends to the actual needs and requirements of local health personnel in low-income countries. The success of this research project would be a proof a concept allowing further development of microarray techniques towards POC-testing of other medical conditions, and could assist in spreading the availability of good healthcare to the most vulnerable populations.

Project ID

SE-0-SE-29-2015-03217-285-12182

Activity status

2 - Implementation

Aid type

D02 - Other technical assistance

% to Uganda

100.00

Organisations

Funding

Sweden

Extending

The Swedish Research Council

Implementing

Karolinska Institutet

CRS code	%
Medical research (12182)	100.0