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Predicting and treating non-typhoidal Salmonella bloodstream infection in children in sub-Saharan Africa

Unlike in Northern countries, where non-typhoidal Salmonella causes self-limiting diarrhea, non-typhoidal Salmonella is the most common cause of bacterial bloodstream infections in children in sub-Saharan Africa. Case fatality is between 20-30%. Susceptible hosts include children with Plasmodiumfalciparum (Pf) malaria, severe anemia, acute malnutrition, and  HIV infected individuals. Salmonella bloodstream infections are difficult to diagnose due to their non-specific presentation mimicking severe malaria, causing both under- and overtreatment. Besides the fact that evidence-based treatment regimens are non-existent, adequate antibiotic treatment is challenging in resource-limited settings and in a context of rising antibiotic resistance.

As a first work-package of my PhD-research project, I will address the epidemiology of non-typhoidal Salmonella bloodstream infections. Salmonella is on the rise in DR Congo, which is in contrast to the decline of the global Salmonella burden. To understand the emerging pattern, I will analyze the seasonal dynamics of Salmonella bloodstream infection incidence in relation to Plasmodium falciparum malaria incidence and environmental/climate factors.

Secondly, I will focus on the clinical prediction of Salmonella bloodstream infections in children in an area of endemic Salmonella and Plasmodium falciparum malaria. I will develop a clinical diagnostic algorithm based on signs and symptoms and basic laboratory tests (hemoglobin, glycemia, malaria rapid diagnostic tests) in hospital admitted children and examine its validity at the primary care level. In addition, I will perform proof-of-concept testing of salivary cortisol as biomarker for pediatric bloodstream infections in a Plasmodiumfalciparum endemic area.

To conclude, I will provide data to improve the evidence-based management of children admitted with suspected or confirmed Salmonella BSI. After adjustment for health-seeking itinerary and disease severity, I will assess whether the outcome (fever defervescence, in-hospital and post-discharge mortality) of a short intravenous antibiotic course with oral switch is not inferior to the outcome of a full duration intravenous antibiotic course. Furthermore, I will develop a population pharmacokinetic model to define the optimal dose of ceftriaxone in children with severe acute malnutrition with suspected/confirmed BSI.

Date:1 Oct 2018 →  Today
Keywords:Tropical medicine, Public health, Microbiology, Children, Pediatrics, Epidemiology, Diagnostics, Antibiotic treatment, Antimicrobial resistance, Pharmacokinetics, Salmonella
Disciplines:Public health sciences not elsewhere classified, Tropical medicine, Pediatrics, Clinical microbiology
Project type:PhD project