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How diagnostics can drive treatment introduction

Samir Agrawal provides an overview of how diagnostics are used to drive treatment of fungal infections.
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How diagnostics can drive treatment. My name is Samir Agrawal. I’m a haemato-oncologist at St Bartholomew’s Hospital in London. And I’m going to introduce this topic by briefly addressing what does this actually mean when we say diagnostics can drive treatment. And really, there are three broad areas where this applies, and I’ll touch on all of these very briefly for you. So there’s screening, diagnostics, in order to establish the presence or absence of invasive fungal disease, and then diagnostics will tests for monitoring, and perhaps helping with cessation of treatment for invasive fungal disease. So the three tests that we have available, at least in a screening strategy, would be most applicable perhaps to two settings.
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One would be intensive care and one would be the haemato-oncology patient who’s about to receive intensive treatment of one nature or another that’s going to make them at high risk of infection. So in the intensive care unit setting, the assay that’s most often used is the beta-d-glucan assay for detection of invasive candidiasis in the bloodstream. The beta-d-glucan assays is actually a pan-fungal marker. In the haemato-oncology setting, perhaps more frequent is the use of galactomannan for the early diagnosis of invasive aspergillosis. And at least in the latter setting, that assay galactomannan sometimes combined with beta-d-glucan and even potentially a third assay could be used, which is aspergillus PCR performed on blood or serum.
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These tests tend to be performed twice weekly, while the patient is in the hospital, with the aim of making a diagnosis before the patient has clinical signs or symptoms. So that is screening. Now if the tests are negative, then quite simply, we do not entertain the possibility of invasive fungal disease. But if one of the tests is positive, then that can trigger usually not immediately treatment, but then further investigations to try and establish the presence of infection or not. If we take the example of an inpatient who’s received chemotherapy and typically would be neutropenic and on antibiotics for an infection or a suspected infection but they’re not responding.
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In this setting, we begin to consider invasive fungal disease as a possibility and the tests that I’ve just mentioned, so beta-d-glucan, galactomannan, and PCR for aspergillus, performed in this setting are now being used to make a diagnosis. And if the tests are positive in this setting, then that strongly supports the presence of invasive fungal disease and in the context of galactomannan, and of course PCR for aspergillus, this would indicate invasive aspergillosis and appropriate treatment can be started. A much trickier clinical dilemma is if the tests are negative in a scenario the patient who has clinically persistent infection, and the management of that– it goes beyond this little introductory talk.
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And I talked about a third setting, which is monitoring of response and use of the biomarkers, the tests that we have for cessation of treatment and response to treatment. Now, for example, a patient who’s galactomannan is positive, as in the formal diagnosis of invasive aspergillosis, that assay can be used to monitor response to treatment. With a falling galactomannan indicating response, and, in particular, a galactomannan that’s increasing, indicating a very poor outcome and the need for further treatment or further investigation. So I congratulate you on doing this course. I hope you’re going to find this module extremely interesting. Please do share your experiences, your comments, with the rest of the group. Thank you.

In this video, Samir Agrawal explains the importance of diagnostics in driving treatment of invasive fungal infections.

The use of diagnostics can be grouped into three categories – screening, diagnosis, and cessation/continuation of treatment.

  • Screening aims to assist with patient diagnosis before they present with clinical signs or symptoms

  • Diagnosis involves the use of tests in patients who have a clinically presenting infection

  • Cessation/continuation focuses on testing patients who have had a diagnosis, with the aim of tracking if their infection is improving or if further investigation and treatment is required

The use of fungal diagnostics is most effective when tests are rapid, sensitive and specific. Use of agar to grow fungi can take 1-20 days, which can delay vital treatment. Due to this, a focus has been placed on developing rapid testing systems such as antigen and nucleic acid-based molecular diagnostics. When used effectively they can reduce mortality and hospital costs, as well as decreasing the use of inappropriate treatment options.

It is vital that effective and affordable diagnostic options are available to all, as this will allow for more effective treatment of invasive fungal infections.

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