Imaging infections

November 11, 2016

Infectious diseases are an important cause of death worldwide. When efficient treatment is available, its efficacy depends on a rapid and correct diagnostic.

Very often, infectious diseases induce similar symptoms to non-infectious inflammatory diseases, making it difficult to choose the right therapy. However, imaging methods such as x-rays, computed tomography (CT), and magnetic resonance imaging (MRI) are already used for diagnosing infections. Despite that, most of these methods are not able to differentiate between inflammatory (not caused by a microorganism) and infectious diseases (caused by pathogens such as bacteria and viruses). This brings a strong need for developing new, and improving current imaging methods to diagnose and follow-up the evolution of infectious diseases.


Medical needs


Pathogen Identification: Infections can be caused by different groups of pathogens such as bacteria, viruses, fungi, and parasites. Each pathogen type induces a different response from our body, and consequently requires different medicines to limit the infection. For example, generally, antibiotics are given to treat bacterial infections but not viral ones. Therefore, identifying the type of microorganism causing the disease is critical to choosing and starting the treatment against it. Thus, the development of tests that would help make this choice in a more efficient manner is an important medical need.
Timing: Another important medical need concerns the timing to get the results on the identification of the pathogen. Tests for identifying the bacteria and finding an effective antibiotic against them are available, but in some cases the results from these tests are not ready in less than 1 day. In most of the cases, the time without adequate treatment means disease aggravation and progression.
Identification of the focus of the infection: Symptoms such as cough and difficulty to breath would be easily associated to respiratory diseases. However, in some cases, the focus of the infection cannot be estimated based on the patient’s clinical symptoms. In this case, an imaging method that could “scan the patient” and give insightful information of the disease focus or multiple foci would indicate an appropriate treatment to this patient.
Invasiveness: An important point to be considered is that patients with infectious diseases might be susceptible to other diseases. Immunosuppressed patients are often affected by infectious diseases due to their inability to mount a proper immune response against the infecting microorganisms. For this reason, invasive tests are not a good option for diagnosing diseases in these patients due to the high risk of infection. Thus, the imaging diagnostics would be a less risky (non-invasive) alternative that would allow choosing the right therapy in a quicker way.
Treatment Follow-up: Another medical need is to have an adequate means to follow-up treatment progress. This helps monitor the cure of the disease in order to prevent unnecessary administration of said medicines and its possible side effects.



Advantages of imaging methods


In summary, the advantages of an ideal imaging method for infectious diseases would be: ability to quickly identify the focus of the infection in a non-invasive manner; identification of the pathogen causing the disease and help with choosing the right therapy and its follow-up.

Additionally, the advantages of imaging for preclinical studies (the ones performed in laboratory animals) are also very relevant. In addition to the advantages in the search for new therapies, the imaging methods would also allow the replacement and/or reduction of laboratory animals used in studies. This would, as a result, significantly improve the quality of the studies and possibly result in better translation of the preclinical studies to the clinical ones.



Advances on imaging methods


Although there is still a lot to be done, the scientific community is engaged in searching for such methods and optimizing old ones. One good example is the adaptation of a contrast material used for PET-CT imaging (positron-emission tomography-computed tomography). Currently used to identify cancer cells and inflamed areas, this contrast material has been modified to be taken up and metabolised by bacteria from the Enterobacteriaceae family, composed by Gram-negative bacteria, such as Klebsiella pneumonia, Salmonella typhimurium and Pseudomonas aeruginosa. The injection of this contrast material in laboratory animals has allowed the detection of the aforementioned bacteria. This contrast material is now being clinically tested, and if approved, could be used in humans.

Another improvement was made on the detection of Aspergillus fumigatus, a fungus that causes lethal infections in humans. The attachment of a specific antibody to a contrast material used in PET-MR had promising, yet not perfect results when detecting this fungal infection in laboratory animals.
Therefore a stronger effort and bigger investments in the development and improvement of imaging methods for diagnosing infectious diseases would certainly pay-off with better quality of life for patients!

References:
Yao, S et al., 2016 – Nuclear Medicine and Biology
Weinstein, EA et al., 2014 – Science Translational Medicine
Rolle, AM et al., 2016 - PNAS