The overall goal of INFECT is to advance our understanding of the pathophysiological mechanisms, prognosis, and diagnosis of the multifactorial highly lethal necrotizing soft tissue infections (NSTIs). NSTI’s are rapidly spreading infections that may cause extensive soft tissue or limb loss, multiorgan failure and are associated with a considerable fatality rate. It is undisputed that rapid diagnosis and prompt intervention is directly related to survival. The initial presentation may be limited to unspecific symptoms such as tenderness, swelling, erythema and pain. Thus, diagnosis and management are difficult due to heterogeneity in clinical presentation, in co-morbidities and in microbiological aetiology. There is an urgent need for novel diagnostic and therapeutic strategies in order to improve outcome of NSTIs. To achieve this, a comprehensive and integrated knowledge of diagnostic features, causative microbial agent, treatment strategies, and pathogenic mechanisms (host and bacterial disease traits and their underlying interaction network) is required.
INFECT was designed to obtain such insight through an integrated systems biology approach in patients (WP2) and different clinically relevant experimental models (WP1 and WP6). The work flow includes a comprehensive set of analyses (WP3 and WP5) followed by integration of results in advanced computational platforms, which enabled generation of pathophysiological models of the disease (WP4) and advanced understanding of the underlying mechanisms and hots-pathogen interactions. The results were translated into novel diagnostic tests (WP7) and improved patient management (WP2 & 8). The work was conducted by the INFECT consortium, which consisted of a team of multidisciplinary researchers, clinicians, SMEs and a patient organization, each with a unique expertise, technical platform and/or model systems that together provided the means to successfully conduct the multifaceted research proposed and efficiently disseminate/exploit the knowledge obtained.
Key achievements of INFECT include:
- Establishment of the world’s largest NSTI patient cohort with extended clinical registry and associated biobank providing a unique resource for the proposed studies.
- Advanced insight into the clinical aspects of NSTIs providing the basis for evidence-based guidelines for patient management and care.
- The systems medicine analyses within INFECT have substantially advanced our understanding of these life-threatening infections, including the identification of novel pathogenic mechanisms and specific host and bacterial disease traits associated with disease outcome.
- The results demonstrate that the pathophysiology of NSTI are influenced both by the causative microbe and by host factors, underscoring the need for patient stratification and implementation of tailored therapy/personalized medicine in these infections.
- Multiplex diagnostic tools for rapid pathogen identification and monitoring of disease associated biomarkers have been developed and tested in the clinical setting.
- The novel understanding of the disease mechanisms of these infections has resulted in changed clinical practice related to antibiotic usage as well as use of immunomodulatory treatments.
- Fostering the new generation of clinical and preclinical scientists within the field of systems medicine in infectious diseases.
Overall, INFECT has proven the value of systems medicine approaches in acute infectious diseases to achieve improved diagnostics and therapeutics to improve patient disease outcome.