Research led by Manchester identifies test to more accurately diagnose rare fungal pneumonia

New research from Manchester University NHS Foundation Trust (MFT) and co-funded by the National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre (BRC), has shown that a DNA-based test is accurate for diagnosing fungal pneumonia caused by Pneumocystis jirovecii in people with weakened immune systems. 

Dr Riina Richardson, Head of Service at the Mycology Reference Centre Manchester based at Wythenshawe Hospital, part of MFT, led an international team of scientists and medical doctors across nine different countries looking at 55 studies containing more than 11,000 test results. 

Their newly published statistical analysis combined all the available data on a DNA-based test called polymerase chain reaction (PCR) from the past 10 years and revealed the accuracy of this test, which has potential impact to improve detection of this fungal pneumonia, across the world.  

Dr Richardson, who is part of Manchester BRC’s Respiratory Theme, where researchers are investigating better ways to diagnosis respiratory infections, said: “Although Pneumocystis pneumonia is rare, it is a common concern for patients with severely weakened immune systems. It is a severe, aggressive infection, and if left untreated, is fatal. It is tricky to diagnose because it cannot be cultured in the laboratory and is easy to miss under the microscope. Therefore, many patients get treated based on clinical concern. 

“It is a fungus we can carry in our airways without it causing disease but in people with a weakened immune system, it can cause infection. Our research shows that Pneumocystis PCR is highly (more than 98 per cent) sensitive and can accurately tell if someone is only carrying the fungus and it has not caused infection, or if it is the cause of their symptoms. In practice, a positive test result on a sample taken from deeper inside the lungs means that the patient has Pneumocystis pneumonia whilst a negative result means that they don’t. This may sound obvious, but few diagnostic tests perform this well.” 

She added: “This type of test is broadly available in the NHS but it has not been clear what sample types should be used for testing for Pneumocystis pneumonia and how reliable the results are. Our statistical analysis will directly answer these questions and help clinicians to make better treatment decisions.” 

Globally, pneumocystis affects around half a million people each year, of whom 42 per cent will die*. Only around  one in five people who are tested turn out to have the infection**. Pneumocystis pneumonia cases have also been rising in England, from about 150 cases annually in 2000, to around 2,680 cases by 2021-22***.  

In the UK, most cases are seen in patients being treated for cancer and receiving bone marrow and solid organ transplants or who are otherwise severely immunocompromised, whilst globally Pneumocystis pneumonia is particularly common in patients living with untreated HIV. 

Dr Richardson said: “It is not completely clear why cases of Pneumocystis pneumonia are increasing in England, but the major contributing factor is that we have more immunocompromised patients at risk of it. We now have better treatments for conditions that used to be life-threatening, and the side effect of many of these treatments is that patients have a weakened immune system.” 

She added: “In the era of antimicrobial resistance threatening patients’ lives, tests that can help clinicians to avoid treating patients unnecessarily are as important as those that diagnose infection. 

“Previously there have been historical difficulties in diagnosing this infection. Our study highlights a new direction in diagnosis, but also signposts where treatment is inappropriate and unnecessary if patients do not have confirmed disease. So, providing that definitive diagnosis is quite radical and the practical implications of this are massive for patient care for this infection.” 

The international group of scientists working on this is a sub-group of the Fungal PCR Initiative (FPCRI), as part of The International Society for Human and Animal Mycology. 

Dr Richardson and the team are now hoping to disseminate their findings globally and are reaching out to clinicians and laboratory staff around the world to encourage them to implement these recommendations.  

The data analysis on PCR testing for Pneumocystis was published in the journal Clinical Infectious Diseases in June 2024. Results were also presented at the ESCMID Global Congress in Barcelona in April 2024.