A recent laboratory-based observational study published in The Journal of Infectious Diseases has shed light on the causes of fevers of unknown origin (FUO) in sub-Saharan Africa, particularly during the major Ebola outbreak in 2014. Conducted by researchers from the Deutsches Zentrum für Infektionsforschung (DZIF) in collaboration with medical professionals from Guinea and Slovakia, this study examined 550 patients in Guinea who exhibited persistent fever but tested negative for the Ebola virus.

Understanding Fever of Unknown Origin

Fever is a common symptom associated with a plethora of diseases, including infections, cancer, and autoimmune disorders. When fever persists without a clear diagnosis following extensive investigation, it is classified as fever of unknown origin (FUO). Globally, approximately half of FUO cases remain undiagnosed, which poses significant challenges for effective treatment.

In the context of sub-Saharan Africa, malaria often becomes the assumed diagnosis—treated without laboratory confirmation. Yet, research indicates that there are about 90 million pediatric hospitalizations annually due to fevers not caused by malaria but by other infectious diseases. This underscores the need for thorough diagnostic approaches to identify the true causes.

Study Methodology

The research conducted by the DZIF team was retrospective and utilized a multifaceted approach, combining epidemiological, phylogenetic, molecular, serological, and clinical data to investigate the infectious agents present in acute febrile patients. The team employed modern diagnostic techniques, including:

  • Serologic tests
  • Polymerase Chain Reaction (PCR)
  • High-throughput sequencing

Findings of the Study

From the analysis, at least one pathogen was identified in 275 out of 550 patients. The pathogens detected offered significant insights into the diverse origins of FUO:

Pathogen Type Detection Rate Note
Malaria Parasite (Plasmodium) Commonly detected Expected finding due to endemicity
Bacterial Infections (e.g., Salmonella, Klebsiella) Detected in ~20% of patients Not typically identified as FUO
Highly Pathogenic Viruses Detected in ~6% of patients Included Yellow Fever and Lassa viruses
Orungo Virus Noted but poorly characterized Lymphocytic choriomeningitis considered

Moreover, the study found concerning levels of antibiotic resistance: one in five infected patients presented with multiple infections, indicating a high rate of co-infections. Specifically, both malaria and bacterial sepsis presented concurrently in approximately 12% of adults and 12.5% of children.

Implications of Findings

The study highlights a crucial issue in diagnostic and treatment methodologies in sub-Saharan Africa. The dominant trend of misdiagnosing FUO cases as malaria leads to inadequate treatment responses. According to Prof. Jan Felix Drexler, the study's lead author:

“In Africa, febrile illnesses of unknown cause are often recognized and treated as malaria without further diagnosis. In our study, we were able to detect a pathogen in about half of all patients with FUO.”

Call for Improved Laboratory Capacities

The findings emphasize the urgent necessity to bolster laboratory capabilities in the region. Prompt identification of infectious causes is essential for:

  • Effective outbreak response
  • Development of regionally appropriate diagnostics
  • Informed treatment regimens

Prof. Drexler advocates for a discussion on region-specific treatment protocols and the necessity for enhanced laboratory infrastructures, stating that this is vital for guiding targeted translational research and improving point-of-care diagnostics.

Further Reading

For additional insights, consider the following sources:

Citation: Ignacio Postigo-Hidalgo et al, Elucidating Infectious Causes of Fever of Unknown Origin: A Laboratory-Based Observational Study of Patients with Suspected Ebola Virus Disease, Guinea, 2014, The Journal of Infectious Diseases (2024).