New Research Illuminates Causes of Fever of Unknown Origin in Sub-Saharan Africa

Recent research conducted by a collaborative team from the German Center for Infection Research (DZIF) and Charité--Universitätsmedizin Berlin has provided valuable insights into the causes of fevers of unknown origin (FUO) in sub-Saharan Africa. This laboratory-based observational study involved a comprehensive analysis of 550 patients in Guinea who experienced persistent fevers during the 2014 Ebola outbreak, despite testing negative for the Ebola virus.

The primary objective of this research was to utilize advanced diagnostic techniques to uncover the underlying infectious diseases responsible for these unexplained fevers. The findings of this study have been published in The Journal of Infectious Diseases.

Fever is a prevalent symptom associated with numerous medical conditions, including infections, malignancies, and autoimmune disorders. When the etiology of a persistent fever remains undetermined after extensive evaluation, it is classified as FUO. Alarmingly, around 50% of FUO cases worldwide remain undiagnosed.

In sub-Saharan Africa, malaria is often presumed to be the cause of fever, leading to treatment without laboratory confirmation. However, it is estimated that 90 million pediatric hospitalizations annually in this region are attributed to fevers caused by various infections other than malaria, frequently resulting from diverse bacterial and viral pathogens.

For this study, the research team employed a retrospective approach to investigate the pathogen diversity among patients in Guinea suffering from FUO during the Ebola crisis in 2014. They integrated epidemiological, phylogenetic, molecular, serological, and clinical data to achieve a comprehensive understanding of the infectious agents involved.

The study revealed that pathogens were identified in 275 of the 550 patients, utilizing serological tests, PCR, and high-throughput sequencing techniques. In addition to the anticipated malaria parasite, Plasmodium, pathogenic bacteria such as strains of Salmonella and Klebsiella were found in nearly 20% of the patients examined.

Concerningly, the research highlighted a significant prevalence of antibiotic resistance within the samples analyzed, alongside a high incidence of co-infections. Notably, 20% of infected individuals presented with multiple simultaneous infections, with co-occurrences of malaria and bacterial sepsis being particularly frequent, affecting 12% of adults and 12.5% of children.

Furthermore, infections involving highly pathogenic viruses were also identified, with yellow fever, Lassa, and Ebola viruses detected through RT-PCR in approximately 6% of patients. Of particular interest was the identification of the Orungo virus, a lesser-known pathogen lacking robust diagnostic assays.

Additionally, the researchers employed immunofluorescence assays, which revealed the presence of IgM antibodies against several viruses, such as those causing Dengue, West Nile, and Crimean-Congo hemorrhagic fever, in patients who were PCR-negative.

The findings underscore a critical issue: febrile illnesses of unknown origin are frequently misidentified as malaria in Africa, leading to inadequate treatment measures. The study demonstrated that pathogens could be detected in roughly half of the FUO patients, revealing the presence of bacterial pathogens responsible for sepsis, hemorrhagic fever viruses, including Ebola, and various strains of malaria.

These results highlight the urgent need to bolster laboratory capacities across sub-Saharan Africa. Early identification of infectious causes behind FUO is essential for improving patient care, effectively managing outbreaks, and developing regionally tailored diagnostic tools.

In conclusion, the research emphasizes the importance of discussing region-specific treatment protocols, enhancing quality control during outbreaks, and utilizing the knowledge of pathogen diversity to improve regional laboratories and foster translational research aimed at point-of-care testing.