Identifying life-threatening infections linked to immune system errors

Life-threatening Infection in Humans: from Epidemiological Analysis to Molecular Genetics

This study is trying to find out how common life-threatening infections are in people with immune system problems to help doctors diagnose and treat them better.

Quick facts

• Study type: Observational
• Enrollment: 360 (estimated)
• Sex: All
• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna (Academic / other)
• Locations: 6 sites (Bologna, Bologna and 5 other locations)
• Trial ID: NCT06775496 on ClinicalTrials.gov

What this trial studies

This observational study aims to identify and calculate the prevalence of cases associated with congenital errors of immunity (ECI) among patients hospitalized with severe infections. It focuses on the clinical and laboratory characterization of these patients, who may present with life-threatening infections caused by various pathogens. The study seeks to improve early diagnosis and individualized treatment, which is crucial for managing these high-morbidity and high-mortality conditions. Patients with both immunological and non-immunological diseases will be included to better understand the spectrum of life-threatening infections.

Who should consider this trial

Good fit: Ideal candidates for this study are otherwise healthy patients who present with life-threatening infections caused by known or unknown pathogens.

Not a fit: Patients with chronic non-immunological diseases or those with secondary immunodeficiencies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to earlier diagnosis and more effective treatments for patients with life-threatening infections linked to immune deficiencies.

How similar studies have performed: Other studies have shown success in identifying and characterizing congenital errors of immunity, suggesting that this approach may yield valuable insights.

Eligibility criteria

Inclusion Criteria:

* Obtained informed consent;
* Otherwise healthy patient on admission

Infectious episode:

* life-threatening caused by known or unknown etiologic agent including viruses, bacteria, mycobacteria or mycetes (in case of lack of microbiologic isolate if clinical, laboratory, histopathologic and radiologic data, justify an infectious origin)
* or caused by vaccine strains of attenuated vaccines such as Measles, Mumps, Rubella, Yellow Fever.
* or caused by viruses, bacteria, mycobacteria or mycetes with features suggestive of congenital deficiency of immunity, the clinical pictures below refer to known conditions potentially associated with congenital errors of innate immunity

Viral susceptibility:

* ARDS caused by influenza virus type A, Sars-Cov2
* Life-threatening enterovirus rhomboencephalitis
* Life-threatening infection by VZV, CMV, EBV, Rhinovirus, Respiratory Syncytial Virus
* HSV encephalitis
* Fulminant hepatitis from HAV
* Kaposi\'s sarcoma from HHV8
* Beta-HPV infections such as: epidermodysplasia verruciformis, mucocutaneous carcinoma,recurrent/diffuse skin warts,, papillomatosis.

Susceptibility to pyogenic bacteria:

* At least one life-threatening infection or two episodes of invasive infectionsin otherwise healthy patients, either systemic (bacteremia) or focal (pneumonia, meningitis, arthritis, osteomyelitis, deep brain/peritoneal/hepatosplenic/muscle abscesses)
* At least two episodes of disseminated or severe staphylococcal muco-cutaneous infections in otherwise healthy patients: decalvant folliculitis, pustules, furunculosis, blepharitis, lymphadenitis, abscesses

Susceptibility to Tropherymawhipplei:

\- Whipple\'s disease

Susceptibility to Mycobacteria:

* Life-threatening , recurrent, or persistent infections with tuberculous or nontuberculous mycobacteria in otherwise healthy patients
* Post-vaccinal BCG-osis from attenuated M. Bovis strain

Susceptibility to mycetes:

* Chronic muco-cutaneous candidiasis Invasive fungal infections of sinuses, lungs, CNS, bones, joints, liver, spleen, and mucocutaneous membranes by Coccidioides, Paracoccidiodes, Cryptococcus, Histoplasma, Pneumocystis, Aspergillus, Talaromyces, Mucormycetes, or Blastomyces
* Invasive candidiasis of brain, eyes, heart, bone, and blood in the absence of central catheters
* Blood dissemination of fungal pathogens (except for candidiasis from central access)
* Persistent positive fungal culture after adequate therapy in terms of drug susceptibility, dosage and duration
* Deep infection with dermatophytes (Microsporum, Epidermophyton, Tricophyton) at dermal and lymph node level
* Infection with rare yeasts (Geotrichum, Kodamaea, Malassezia/Rhodotorula, Saccharomyces, Trichosporon) or rare molds (AureobasidiumChrysosporium, Corynesprora, Exophiala, Geosmithia, Ochroconis, Paecilomyces, Phellinus, Phialophora, Rhizopus, Scopulariopsis)

Other:

-All infectious diseases not included in the list whose natural history differs from that expected for the identified pathogen with regard to severity, recurrence, and persistence of the disease, if the condition is not otherwise explainable by the patient\'s acquired risk factors.

Exclusion Criteria:

* Patients with nonimmunological diseases, secondary immunodeficiencies, nonpharmacological iatrogenic factors, immunosuppressive drug therapies

Where this trial is running

Bologna, Bologna and 5 other locations

• IRCCS Istituto delle Scienze Neurologiche — Bologna, Bologna, Italy (Recruiting)
• IRCCS Azienda Ospedaliero Universitaria di Bologna UO Pediatria — Bologna, Bologna, Italy (Recruiting)
• IRCCS Azienda-Ospedaliero Universitaria di Bologna UO Anestesiologia e Rianimazione generale e pediatrica — Bologna, Bologna, Italy (Recruiting)
• IRCCS Azienda-Ospedaliero Universitaria di Bologna UO Malattie Infettive — Bologna, Bologna, Italy (Recruiting)
• IRCCS Azienda-Ospedaliero Universitaria di Bologna UO Neonatologia e terapia intensiva neonatale — Bologna, Bologna, Italy (Recruiting)
• IRCCS Azienda-Ospedaliero Universitaria di Bologna UO Pediatria d'Urgenza, Pronto Soccorso e Osservazione Breve e Intensiva — Bologna, Bologna, Italy (Recruiting)

Study contacts

• Principal investigator: Daniele Zama, MD — IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Study coordinator: Daniele Zama, MD

Conditions Life-threatening Infection