Should a breathless child with fever be treated with antibiotics in case they have pneumonia? Emergency doctors face this dilemma many times a day, and it takes more than 24 hours to get a definite answer.
Faced with a patient who could die without treatment, doctors tend to err on the side of caution.
But over-prescription of antibiotics is causing the bacteria to build up resistance, making treatment ineffective.
Now Dr Climent Casals-Pascual, a researcher at the Wellcome Trust Centre for Human Genetics in Old Road, Headington, has discovered a protein ‘clue’ that can diagnose pneumonia caused by bacteria in minutes.
He hopes to add this to a malaria test which he developed earlier.
He said: “Eventually we hope to combine all these markers into one test for pneumonia and malaria. We are quite excited about the future. The idea is to be able to measure several things in a single drop of blood, and doctors can then decide whether they want to give antibiotics and/or anti-malarials.
“Anything that has a real impact in terms of reducing the amount of antibiotics we give out, has to be good."
Dr Climent Casals-Pascual spent nearly five years in Africa before joining the Wellcome Trust Centre, a research institute of the Nuffield department of medicine at Oxford University, funded by the university, the Wellcome Trust and other sponsors
He said: “You have 24 hours to make a diagnosis. By that time, some patients might die, so a diagnostic technique is incredibly important.”
Dr Casals-Pascual, a native of Barcelona, travelled to Kenya as part of the research for his Oxford doctorate, and returned determined to solve the problem.
With a grant from the Medical Research Council, he worked with researchers in The Gambia to identify the protein associated with severe malaria, identifying 8,905 protein fragments in blood plasma from patients with mild or severe malaria.
Next he turned his attention to pneumonia. He and his researchers found the protein biomarker by a painstaking and detailed comparison of blood samples from 390 children in Gambia with and without pneumonia.
Dr Casals-Pascual said: “Making a quick and accurate diagnosis can have a major impact on the outcome for all children with pneumonia.
“Pneumonia can be caused by viruses or by bacteria. The critical question is to identify those pneumonia cases caused by bacteria, so that antibiotics can be given immediately.
“This test will be particularly important for children in remote areas or in the developing world where an X-ray or blood culture diagnosis is rarely available.”
Not only is there more antibiotic resistance in tropical countries, but there is also less expertise in diagnosis.
Some patients have the two diseases simultaneously, he said. “If you get it wrong you have 24 hours and then you die, and that's why people err on the side of safety and over-prescribe.”
He added: “This biomarker can be developed into a test that is faster and more sensitive than blood cultures or x-rays.
“We can also use this test to distinguish between those children who are breathless with malaria and those with pneumonia, and treat each child quickly and appropriately. Do they need to go to hospital, or do I send them home with antibiotics and/or
anti-malarials? We can answer that question.”
Dr Casals-Pascual received funding from the Medical Research Council to work in collaboration with the MRC Unit, The Gambia, to identify these new biomarkers and with the KEMRI Wellcome Trust Unit in Kilifi, Kenya, to validate the findings.
Pneumonia causes more than a million deaths every year in under fives, according to the World Health Organisation, and accounts for 18 per cent of all such deaths worldwide. Delayed diagnosis is a major risk factor.
In sub-Saharan Africa, malaria and septicaemia are also commonly associated with respiratory distress in children, making diagnosis difficult.
At the moment, diagnosis involves growing bacteria in the lab, taking at least
24 hours, and lack of microbiology facilities in developing countries – and in primary care or after-hours clinics in developed countries – limits rapid diagnosis.
The rapid pneumonia tests using the biomarkers are aimed at replacing
time-consuming and labour-intensive methods, giving a diagnosis within hours.
Dr Casals-Pascual's team's research paper — Discovery and Validation of Biomarkers to Guide Clinical Management of Pneumonia in African Children — is published in leading journal Clinical Infections Diseases.
Now Oxford University's technology commercialisation company, Isis Innovation, is hoping a diagnostics company will take on the rights to develop and manufacture a blood test kit.
Dr Casals-Pascual said he was confident of finding funding to develop the test. “Once we have the science, I am confident that we will get further funding.”