By IDSE News Staff
A new retrospective, laboratory-based observational study provides detailed insights into the causes of fever of unknown origin (FUO) in sub-Saharan Africa.
Scientists examined 550 patients from Guinea who developed a persistent fever at the time of the major Ebola outbreak in 2014, but tested negative for the Ebola virus on-site. The goal was to use modern diagnostic methods to better understand the underlying infectious diseases (J Infect Dis 2025 Feb 10. doi:10.1093/infdis/jiae637).
Approximately half of all FUO cases worldwide remain undiagnosed. In sub-Saharan Africa, malaria is often suspected and treated without laboratory confirmation or further investigation. However, 90 million pediatric hospitalizations per year in sub-Saharan Africa are due to fevers not caused by malaria but by other infections, often bacteria and viruses.
A research team from the German Center for Infection Research (DZIF) and Charité—Universitätsmedizin Berlin, with scientists from Guinea and Slovakia, conducted a retrospective observational study to investigate the pathogen diversity among these patients with FUO. They combined epidemiological, phylogenetic, molecular, serological and clinical data.
At least one pathogen was detected in 275 of 550 patients with serological tests, polymerase chain reaction (PCR) and high-throughput sequencing. In addition to the expected malaria parasite Plasmodium, pathogenic bacteria such as Salmonella and Klebsiella strains were detected in almost one-fifth of the patients. The frequent detection of resistance to first-line antibiotics in the samples examined and the high rate of coinfections were also worrying: 1 in 5 infected patients had multiple infections. Pathogens causing malaria and bacterial sepsis were particularly common, occurring together in 12% of adults and 12.5% of children.
Infections with highly pathogenic viruses were also common: Yellow fever, Lassa and Ebola viruses were detected by real-time PCR in about 6% of patients. Of particular note was the detection of infection with Orungo virus, a little-known pathogen for which there are no robust assays. Using immunofluorescence assays, the researchers also identified immunoglobulin M (IgM) antibodies against several viruses, including dengue, West Nile and Crimean-Congo hemorrhagic fever viruses, in patients who were PCR-negative.
“In our study, we were able to detect a pathogen in about half of all patients with FUO, including bacterial pathogens that cause sepsis, hemorrhagic fever viruses including Ebola and, as expected, various strains of the malaria parasite Plasmodium,” explained the study’s last author Jan Felix Drexler, PhD, a virologist with Charité—Universitätsmedizin Berlin.
The findings underscore the urgent need to strengthen laboratory capacity in sub-Saharan Africa. Early detection of the infectious causes of FUO is critical for patient care, effective response to outbreaks and development of regionally appropriate diagnostics.
“Our results show that regionally adapted treatment regimens should be discussed that quality control in the context of outbreaks needs to be strengthened, and that knowledge of the pathogen spectrum can guide targeted strengthening of regional laboratories and translational research in the sense of point-of-care tests,” Dr. Drexler said.
