The Masanga Fever Study (MaFeStu): a prospective hospital-based observational study of causes of febrile illness in rural Sierra Leone

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Background Febrile illness is a leading cause of hospital admission in West Africa. Accurate diagnosis guides treatment, yet diagnostic capacity remains limited, especially in rural settings. We aimed to identify causes of febrile illness requiring hospital admission in rural Sierra Leone using a diagnostic algorithm designed to strengthen local laboratory capacity, and to describe the spectrum of pathogens, their antimicrobial susceptibility, and the diagnostic yield of the implemented investigations. Methods We conducted a prospective, hospital-based observational study in rural Sierra Leone, from September 26, 2023, to September 26, 2024. Patients were eligible if aged ≥5 months, screened within 3 h of admission, and had tympanic temperature >37.5 °C or reported fever within 72 h. A context-appropriate diagnostic algorithm guided core and symptom-directed testing, including rapid diagnostic tests, microscopy, culture-based diagnostics, imaging and additional investigations as required. Clinical history, examination findings, vital signs, laboratory results, and discharge diagnoses were recorded by trained study staff. The primary outcome was the final diagnosis of acute febrile illness, assigned by study physicians using standard clinical criteria supported by the diagnostic algorithm. Secondary outcomes included identified pathogen, antimicrobial resistance rates, and diagnostic yield. Findings Of 901 patients screened, 756 were enrolled. The most frequent diagnoses were malaria (234/756, 31.0%, 95% CI 27.8–34.3), skin and soft tissue infections (158/756, 20.9%, 95% CI 18.2–23.9), digestive system infections (156/756, 20.6%, 95% CI 17.9–23.7), and lower respiratory tract infections (143/756, 18.9%, 95% CI 16.3–21.9). Commonly identified pathogens included Plasmodium spp. (n = 194), Enterobacterales (n = 135), Mycobacterium tuberculosis complex (n = 50) and Staphylococcus aureus (n = 46). Ceftriaxone resistance among Enterobacterales was 75.2% (85/113), and Extended-Spectrum β-Lactamase production was observed in 74.3% (26/35) of Escherichia coli and 83.8% (31/37) of Klebsiella spp. isolates. Overall, 61.2% (463/756) of patients had a confirmed diagnosis, and a pathogen was identified in 47.2% (357/756) of patients. Interpretation Context-appropriate diagnostics can be integrated into rural West African hospitals, enabling real-time diagnosis of febrile illness. Our findings show an under-recognised burden of skin and soft tissue infections and highlight the need to address antimicrobial resistance, particularly in Gram-negative infections. Strengthened diagnostic capacity is essential to guide treatment and policy. Funding Centre of Tropical Medicine and Travel Medicine, Amsterdam UMC, location University of Amsterdam, Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ)/Klinikpartnerschaften (project: 81281918 and 81307656).