Clinical trial NCT04473768: Clinical Decision Support in Non-typhoidal Salmonella Bloodstream Infections in Children
Official title: Clinical Decision Support in Non-typhoidal Salmonella Bloodstream Infections in Children in Sub-Saharan Africa: a Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: Institute of Tropical Medicine, Belgium
Sponsor class: OTHER
Collaborators: name: KU Leuven
name: Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
name: Hôpital St. Luc Kisantu, République Democratique du Congo
name: International Vaccine Institute
First posted: 2020-07-16
Enrollment: 1880
Sex: ALL
Minimum age (years): 28
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.


Eligibility criteria: Inclusion Criteria:

1. Be a child of \> 28 days and \< 5 years old
2. Be admitted to Kisantu Hospital
3. 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
4. Having a caregiver willing and able to provide written informed consent

Exclusion Criteria:

* None

Primary outcomes:
measure: Predictive signs and symptoms
timeFrame: 12 months
measure: Contribution of handheld diagnostics and point-of-care tests to NTS bloodstream infection diagnosis
timeFrame: 12 months
measure: Clinical decision support model for NTS bloodstream infection
timeFrame: 12 months
Secondary outcomes:
measure: Contribution of handheld diagnostics and point-of-care tests to bloodstream infection diagnosis
timeFrame: 12 months
measure: Clinical decision support model for bloodstream infection
timeFrame: 12 months
measure: Case fatality
timeFrame: 12 months
measure: Geographical clustering
timeFrame: 12 months
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Kisantu general referral hospital
Study officials:
affiliation: Institute of Tropical Medicine
name: Bieke Tack, MD
role: PRINCIPAL_INVESTIGATOR
References: