Clinical Decision Support in Non-typhoidal Salmonella Bloodstream Infections in Children

NCT04473768 | Completed

• 1 other identifier: ID ITM202007
• Study Type: observational
• Target: 1,880
• Locations: 1 country
• Sites: 1

Brief Summary

In sub-Saharan Africa, non-typhoidal Salmonella (NTS) are a frequent cause of bloodstream infection, display high levels of antibiotic resistance and have a high case fatality rate (15%). In Kisantu hospital in the Democratic Republic of Congo (DR Congo), NTS account for 75% of bloodstream infection in children and many children are co-infected with Plasmodium falciparum (Pf) malaria. NTS bloodstream infection presents as a non-specific severe febrile illness, which challenges early diagnosis and, as a consequence, prompt and appropriate antibiotic treatment.Moreover, at the first level of care, frontline health workers have limited expertise and diagnostic skills and, as a consequence, clinical danger signs that indicate serious bacterial infections are often overlooked. Basic handheld diagnostic instruments and point-of-care tests can help to reliably detect danger signs and improve triage, referral and the start of antibiotics, but there is need for field implementation and adoption to low-resource settings. Further, it is known that some clinical signs and symptoms are frequent in NTS bloodstream infections. The integration of these clinical signs and symptoms in a clinical decision support model can facilitate the diagnosis of NTS bloodstream infections and target antibiotic treatment. The investigators aim to develop such a clinical decision support model based on data from children under five years old admitted to Kisantu district referral hospital in the Democratic republic of the Congo. While developing the model, the investigators will focus on the signs and symptoms that can differentiate NTS bloodstream infection from severe Pf malaria and on the clinical danger signs that can be assessed by handheld diagnostic instruments and point-of-care tests. The deliverable will be a clinical decision support model ready to integrate in an electronic decision support system.

Conditions

Bloodstream Infection; Salmonella Bacteremia; Malaria,Falciparum; Severe Malaria

Keywords

Bloodstream infection; Salmonella non-typhi; Children under five years; Clinical decision support; Democratic Republic of the Congo; Fever; Febrile illness; Malaria; Anemia; Malnutrition; Bacterial infection

Outcome Measures

Primary Outcomes (3)

• Predictive signs and symptoms

  Identify clinical signs and symptoms predictive for and differentiate between: 1.1. NTS bloodstream infection 1.2. severe Pf malaria mono-infection 1.3. NTS/Pf malaria co-infection 1.4. other-pathogen bloodstream infections 1.5. other causes of febrile illness requiring hospital admission

  12 months

• Contribution of handheld diagnostics and point-of-care tests to NTS bloodstream infection diagnosis

  Assess the contribution of handheld diagnostic instruments and point-of-care tests to the detection of danger signs associated with NTS bloodstream infection

  12 months

• Clinical decision support model for NTS bloodstream infection

  Develop a clinical decision support model for diagnosis of NTS bloodstream infection based on the predictive clinical signs and symptoms associated with NTS bloodstream infections

  12 months

Secondary Outcomes (4)

• Contribution of handheld diagnostics and point-of-care tests to bloodstream infection diagnosis

  12 months

• Clinical decision support model for bloodstream infection

  12 months

• Case fatality

  12 months

• Geographical clustering

  12 months

Study Arms (5)

NTS bloodstream infection

growth of NTS in blood culture

NTS/Pf malaria co-infection

concurrence of current Pf malaria infection and NTS bloodstream infection

Other pathogen bloodstream infections

growth of a pathogen other than NTS in blood culture

Severe Pf malaria mono-infection

defined according to WHO-criteria

Other causes of febrile illness requiring hospital admission

* Current Pf malaria infection: see above * Recent Pf malaria infection: see above * Non-confirmed bloodstream infection without Pf malaria: no growth in blood culture and negative results in all Pf malaria tests * If feasible, severe bacterial localized infections such as pneumonia, meningitis, osteomyelitis, complicated urinary tract infection, abscess, skin/soft tissue infection or abdominal infection, will be assessed and clinically defined

Eligibility Criteria

• Age: 28 Days - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Study site: Pediatric ward of St. Luc general referral hospital in Kisantu health zone (Province Kongo Central, DR Congo), further referred to as "Kisantu Hospital" * Capacity: 100 beds, bed occupancy reaches up to 180% * Financial system: Flat fees per admission (10$) * Ongoing blood culture surveillance study: * Routine free-of-charge blood culture sampling \& work-up coordinated by INRB/ITM * Since 2017, blood culture surveillance as a part of typhoid conjugate vaccine study * Epidemiological context: * High burden of non-typhoidal Salmonella (NTS) bloodstream infections * High Plasmodium falciparum (Pf) malaria endemicity * High prevalence of malnutrition

You may qualify if:

• Be a child of \> 28 days and \< 5 years old
• Be admitted to Kisantu Hospital
• Having a blood cultured sampled according to the criteria for suspected bloodstream infection embedded in the blood culture surveillance, i.e. presence of objective fever, hypothermia or history of fever during past 48 hours + at least one of the following criteria:
• Hypotension, confusion or increased respiratory rate
• Suspicion of severe localized infection: pneumonia, meningitis, osteomyelitis, complicated urinary tract infection, abscess, skin/soft tissue infection or abdominal infection
• Suspicion of typhoid fever
• Suspicion of severe Pf malaria
• Having a caregiver willing and able to provide written informed consent

You may not qualify if:

• None

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• KU Leuven: collaborator
• Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo: collaborator
• Hôpital St. Luc Kisantu, République Democratique du Congo: collaborator
• International Vaccine Institute: collaborator

Study Sites (1)

Kisantu general referral hospital

Antwerp, 2000, Belgium

Location

Related Publications (1)

• Tack B, Vita D, Mbuyamba J, Ntangu E, Vuvu H, Kahindo I, Ngina J, Luyindula A, Nama N, Mputu T, Im J, Jeon H, Marks F, Toelen J, Lunguya O, Jacobs J, Van Calster B. Developing a clinical prediction model to modify empirical antibiotics for non-typhoidal Salmonella bloodstream infection in children under-five in the Democratic Republic of Congo. BMC Infect Dis. 2025 Jan 27;25(1):122. doi: 10.1186/s12879-024-10319-x.

  PMID: 39871187 DERIVED

MeSH Terms

Conditions

Sepsis; Malaria, Falciparum; Malaria; Fever; Anemia; Malnutrition; Bacterial Infections

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Protozoan Infections; Parasitic Diseases; Mosquito-Borne Diseases; Vector Borne Diseases; Body Temperature Changes; Signs and Symptoms; Hematologic Diseases; Hemic and Lymphatic Diseases; Nutrition Disorders; Nutritional and Metabolic Diseases; Bacterial Infections and Mycoses

Study Officials

• Bieke Tack, MD

  Institute of Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: July 16, 2020
• Study Start: February 1, 2021
• Primary Completion: January 31, 2022
• Study Completion: January 31, 2022
• Last Updated: April 5, 2022

Record last verified: 2022-04

Locations

BE (1)