preprint · medRxiv
Surveillance of 392 children presenting with severe febrile illness at a referral hospital in Tanzania revealed bloodstream infections in 5.2 percent of participants, accompanied by a 45 percent case fatality rate. Overall, causative pathogens were detected in 9.8 percent of the children. Whole genome sequencing of blood culture isolates demonstrated that gram-negative bacteria, specifically Escherichia coli and Klebsiella pneumoniae, were the predominant causes. Many of these pathogens carried extended-spectrum beta-lactamase resistance genes, including CTX-M-15 and CTX-M-27, which rendered them resistant to standard first-line antimicrobial therapies. In addition, phylogenetic analysis of tracheal aspirates pointed to probable hospital-acquired transmission among ventilated paediatric patients.
Severe febrile illness in hospitalised children carries a severe risk of death when complicated by bloodstream infections. The presence of antibiotic-resistant bacteria makes standard initial treatments ineffective, leading to poor patient outcomes. Demonstrating the extent of drug resistance and hospital-acquired transmission highlights the necessity of updating local treatment guidelines and improving basic infection prevention in healthcare settings.
This early-stage clinical and genomic research highlights clear targets for developers of diagnostic tools. It underscores the demand for rapid, culture-independent diagnostic devices and point-of-care antimicrobial resistance screening tests for hospital settings. While the findings provide critical local epidemiological data to guide future product requirements, the abstract does not indicate a direct commercial application or product development pathway.
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Abstract We evaluated the prevalence, pathogen profile, and antimicrobial resistance (AMR) patterns of bloodstream infections (BSIs) among 392 children with severe febrile illness who presented (July 26, 2022-September 20, 2023) to a referral hospital in Tanzania. We identified a causative pathogen in 9.8% (n=38) of participants. Blood culture analysis confirmed BSI in 5.2% (n=20) of participants with a case fatality rate of 45%. Whole genome sequencing (WGS) of blood culture isolates identified gram-negative bacteria ( Escherichia coli, Klebsiella pneumoniae ) as the predominant pathogens, many exhibiting extended-spectrum beta-lactamase (ESBL) resistance genes (CTX-M-15, CTX-M-27), rendering them resistant to first-line antimicrobials. We also observed probable nosocomial transmission in ventilated patients based on phylogenetic analyses of tracheal aspirate isolates. There is an urgent need for enhanced AMR surveillance, empiric antibiotic regimens tailored to local AMR patterns, culture-independent diagnostics, and robust infection control practices in resource-limited settings to mitigate BSI-related mortality and minimize nosocomial transmission risk. Funding NIAID K23AI144029 (TBK), NIAID K23AI185326 (VTC), Chan Zuckerberg Biohub (JLD, CRL) Article Summary Line Genomic surveillance of severe febrile illness in Tanzanian children reveals high mortality rates and widespread resistance to first-line antibiotics, highlighting the urgent need for tailored treatments and enhanced antimicrobial resistance monitoring.
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DOI: 10.1101/2025.05.25.25328306
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