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A groundbreaking retrospective, laboratory-based observational study has provided new insights into the causes of fevers of unknown origin (FUO) in sub-Saharan Africa. Conducted by researchers from the German Center for Infection Research (DZIF) at Charité—Universitätsmedizin Berlin, in collaboration with scientists from Guinea and Slovakia, the study examined 550 patients from Guinea who developed persistent fever during the 2014 Ebola outbreak but tested negative for the Ebola virus.
The primary objective of the study, published in The Journal of Infectious Diseases, was to use modern diagnostic techniques to better understand the infectious diseases underlying FUO. Fever is a common symptom associated with infections, cancer, and autoimmune diseases. When extensive testing fails to identify a cause, the condition is classified as FUO. Globally, approximately half of all FUO cases remain undiagnosed.
In sub-Saharan Africa, malaria is frequently suspected and treated without laboratory confirmation. However, an estimated 90 million pediatric hospitalizations each year in the region are due to fevers not caused by malaria but by other bacterial and viral infections.
Study Findings: A Diverse Range of Infections
The research team employed a combination of epidemiological, phylogenetic, molecular, serological, and clinical analyses to investigate the diversity of pathogens among patients with FUO. Using serologic tests, PCR, and high-throughput sequencing, at least one pathogen was identified in 275 of the 550 patients.
As expected, the malaria parasite Plasmodium was commonly detected. However, pathogenic bacteria such as Salmonella and Klebsiella strains were found in nearly 20% of cases. A notable concern was the frequent resistance to first-line antibiotics, as well as the high prevalence of co-infections: one in five infected patients had multiple infections simultaneously. Malaria and bacterial sepsis were particularly common co-infections, occurring in 12% of adults and 12.5% of children.
Additionally, highly pathogenic viruses were detected, including Yellow fever, Lassa, and Ebola viruses, found via RT-PCR in about 6% of patients. The study also identified the presence of Orungo virus, a little-known pathogen for which no robust diagnostic assays currently exist. Further immunofluorescence testing revealed IgM antibodies against Dengue, West Nile, and Crimean-Congo hemorrhagic fever viruses in patients who were PCR-negative.
Implications for Diagnosis and Treatment
“In Africa, febrile illnesses of unknown cause are often treated as malaria without further diagnostic workup. In our study, we identified a pathogen in about half of all FUO cases, including bacterial sepsis, hemorrhagic fever viruses such as Ebola, and various Plasmodium strains,” said Prof. Jan Felix Drexler, the study’s senior author.
The findings highlight the urgent need to strengthen laboratory capacity in sub-Saharan Africa. Early detection of infectious causes of FUO is essential for patient care, outbreak response, and the development of regionally appropriate diagnostics.
“Our results indicate that regionally adapted treatment strategies should be explored, outbreak quality control must be reinforced, and knowledge of the pathogen spectrum can help in the strategic enhancement of regional laboratories and translational research for point-of-care diagnostic tests,” Drexler added.
Conclusion
The study underscores the importance of robust laboratory diagnostics in managing infectious diseases and combating emerging health threats in sub-Saharan Africa. By improving diagnostic capabilities, healthcare providers can better identify and treat febrile illnesses, ultimately improving patient outcomes and mitigating future outbreaks.
Disclaimer: This article is based on a scientific study and is for informational purposes only. It does not constitute medical advice or endorsement of specific treatments. Readers are encouraged to consult healthcare professionals for medical concerns.
