Diagnostic and Prognostic Biomarkers for Childhood Bacterial Pneumonia

NCT ID: NCT03996967

Last Updated: 2022-05-31

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 837 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-02-11
• Study Completion Date: 2021-04-10

Brief Summary

Clinical pneumonia is a leading cause of pediatric hospitalization. The etiology is generally bacterial or viral. Prompt and optimal treatment of pneumonia is critical to reduce mortality. However, adequate pneumonia management is hampered by: a) the lack of a diagnostic tool that can be used at point-of-care (POC) and promptly and accurately allow the diagnosis of bacterial disease and b) lack of a prognostic POC test to help triage children in need of intensive assistance. Antibiotic therapy is frequently overprescribed as a result of suspected bacterial infections resulting in development of antibiotic resistance. Conversely, in malaria-endemic areas, antibiotics may also be "underprescribed" and children with bacterial pneumonia sent home without antibiotic therapy, when the clinical pneumonia is mistakenly attributed to a co-existing malaria infection.

The investigators previously identified combinations of protein with 96% sensitivity and 86% specificity for detecting bacterial disease in Mozambican children with clinical pneumonia. The investigators' prior work showed that it is possible to identify biosignatures for diagnosis and prognosis using few proteins. Recently, other authors also identified different accurate biosignatures (e.g., IP-10, TRAIL and CRP).

In this study, the investigators propose to validate and improve upon previous biosignatures by testing prior combinations and seeking novel combinations of markers in 900 pediatric inpatients aged 2 months to 5 years with clinical pneumonia in The Gambia. The investigators will also use alternative case criteria and seek diagnostic and prognostic combination of markers. This study will be conducted in Basse, rural Gambia, in two hospitals associated with the Medical Research Council Unity The Gambia (MRCG). Approximately 900 pediatric patients with clinical pneumonia aged 2 months to 5 years of age will be enrolled. Patients will undergo standard of care test and will have blood proteins measured through Luminex®-based immunoassays.

Results of this study may ultimately support future development of an accurate point-of-care test for bacterial disease to guide clinicians in choices of treatment and to assist in the prioritization of intensive care in resource-limited settings.

Conditions

Pneumonia, Bacterial; Viral Infection; Clinical Pneumonia; Plasmodium Falciparum Malaria; Malaria; Infections, Respiratory

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

BA Group

The bacterial group: Patients will be assorted to this group if he/she has a bacterial pathogen culture of fluid from a normally sterile site (e.g. blood, pleural fluid)

No interventions assigned to this group

VI Group

The viral group: Patients will be assigned to this group if they have negative bacteria microbiological tests, negative malaria blood slides, X-rays without "endpoint pneumonia", no evidence of fungal infection, and positive PCR for a viral pathogen from nasopharyngeal swabs.

No interventions assigned to this group

MA Group

The malarial group: Patients will be assigned to this group if they have normal X-rays, no bacterial infection and \>0 asexual P. falciparum parasites if they are aged \< 1 year, or \> 2,500 asexual parasites/µl of blood if they are aged \> 1 year

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Pediatric patients aged between 2 months and 5 years presenting at the screening sites with respiratory symptoms, i.e. cough or difficulty breathing AND
• One of the following: Increased respiratory rate for age OR indrawing OR SaO2 < 93% OR grunting OR MUAC < 11.5 if child is greater or equal than 6 months of age OR visible wasting AND
• Referred to clinician review for probable admission

Definition of increased respiratory rate (rr) for age based on the WHO criteria: respiratory rate (rr) > > 50 for 2-11 month old; rr > 40 for 1-5 years old.

• No symptoms or signs of any disease
• No malaria infection as detected by microscopy or RDT
• No history of clinical pneumonia or hospital admission

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

• Suspected tuberculosis based on history of cough lasting > 2 weeks
• Hospital admission in the previous 2 weeks.
• Children that show any evidence of other conditions that could be worsened by blood collection will be further excluded from this study.

• Having received a vaccine within the prior 4 weeks

• Minimum Eligible Age: 2 Months
• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Medical Research Council Unit, The Gambia, LSTMH

UNKNOWN

Sponsor Role: collaborator

Laboratory of Transnational Immunology, UMC Utrecht

UNKNOWN

Sponsor Role: collaborator

Boston University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clarissa Valim, MD ScD

Role: PRINCIPAL_INVESTIGATOR

Boston University

Patricia Hibberd, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Boston University

Locations

Boston University School of Public Health

Boston, Massachusetts, United States

Laboratory of Transnational Immunology, UMC Utrecht

Utrecht, , Netherlands

Basse Field Station, Medical Research Council Gambia Unit

Basse Santa Su, URR, The Gambia

Countries

United States; Netherlands; The Gambia

Other Identifiers

R21AI140258-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

H-38462

Identifier Type: -

Identifier Source: org_study_id