Infectious Etiologies of Febrile Illnesses in Cameron.

Abstract

Background: Diagnosis of febrile illnesses in malaria-endemic countries focuses primarily on confirming or ruling out malaria, since malaria is considered a major health threat. But because of the high rate of malaria over-diagnosis, other febrile illnesses are often misdiagnosed or overlooked. Thus, there remains a large gap in our understanding of pathogen profiling in most malaria-endemic countries. Because knowing the cause of fever is the first step in deciding appropriate treatment and improving disease outcomes, the overall objective of this dissertation research was to identify infectious causes of febrile illnesses in Cameroon. Methods: We recruited 550 febrile patients seeking care at selected hospitals in Cameroon. Blood samples were collected from patients and used to conduct malaria tests by thick film microscopy, rapid diagnostic testing and PCR. Plasma samples were tested for antibodies against dengue, West Nile, chikungunya and respiratory viruses, Leptospira interrogans and Salmonella typhi, using RDT, microsphere immunoassay (MIA) and ELISA. Collected stool samples were cultured for the isolation of Salmonella and Shigella sp. Recombinant proteins of Ebola, Sudan, Marburg and Lassa viruses were expressed using Drosophila S2 cells and used to develop a MIA for viral hemorrhagic fevers (VHF). MIA was pre-validated using human or humanized monoclonal antibodies, and 408 previously collected plasma samples were screened for the presence of IgG antibodies for hemorrhagic fever viruses. Results: Although malaria was the main cause of febrile illnesses in Cameroon, the accuracy of clinical diagnosis of malaria was poor. That is, 38% of the patients clinically diagnosed as having malaria had fever caused by other pathogens, including acute respiratory tract infections, typhoid fever, amebiasis, toxoplasmosis, shigellosis, dengue fever, West Nile fever, and chikungunya virus infection. We developed and pre-validated a multiplex MIA for the diagnosis of VHF, and identified samples (5/408) suspected to be positive for Ebola, Lassa and Marburg viruses. Conclusion: Collectively, our data provide the first evidence of several pathogens causing febrile illnesses in Cameroon and may provide the basis for developing an algorithm for the management of febrile illnesses. This study also reports for the first time the development of a MIA for the diagnosis of VHF.