Pathogens That Cause Acute Febrile Illness Among Children and Adolescents in Burkina Faso, Madagascar, and Sudan

Abstract

Background: The etiology and optimal clinical management of acute febrile illness (AFI) is poorly understood.

Methods: Blood samples taken from study participants with acute fever (≥37.5°C) or a history of fever and recruited into the previous Typhoid Fever Surveillance in Africa (TSAP) study were evaluated using a polymerase chain reaction (PCR)-based TaqMan-Array Card designed to detect a panel of bacterial, viral, and parasitic pathogens. Clinical metadata were also assessed.

Results: A total of 615 blood samples available for analysis originated from Burkina Faso (n = 53), Madagascar (n = 364), and Sudan (n = 198) and were taken from participants ranging in age from 0-19 years. Through the TaqMan-Array Card, at least 1 pathogen was detected in 62% (33 of 53), 24% (86 of 364), and 60% (118 of 198) of specimens from Burkina Faso, Madagascar, and Sudan, respectively. The leading identified pathogen overall was Plasmodium spp., accounting for 47% (25 of 53), 2.2% (8 of 364), and 45% (90 of 198) of AFI at the respective sites. In Madagascar, dengue virus was the most prevalent pathogen (10.2%). Overall, 69% (357 of 516) of patients with clinical diagnoses of malaria, respiratory infection, or gastrointestinal infection were prescribed a World Health Organization guideline-recommended empiric antibiotic, whereas only 45% (106 of 237) of patients with pathogens detected were treated with an antibiotic exerting likely activity.

Conclusions: A PCR approach for identifying multiple bacterial, viral, and parasitic pathogens in whole blood unveiled a diversity of previously undetected pathogens in AFI cases and carries implications for the appropriate management of this common syndrome.

Keywords: Africa/sub-Saharan Africa; TaqMan array; febrile illness; whole blood.

Figure 1.

Quantities of pathogens detected in blood using the TaqMan Array Card. Quantification cycle (Cq) values, an inverse metric of pathogen load, are shown on the y- axis for the different pathogens detected. In this study, the Cq values of most bacterial, fungal, and viral targets ranged from 30 to 40, with a few exceptions of early Cq values such as Bartonella spp., Klebsiella oxytoca, and Enterovirus spp. Therefore, most of these samples had low pathogen loads. Alternatively, low Cq-values could have resulted from sample degradation, in particular, for viral pathogens with RNA genomes, as the whole blood samples used for this retrospective testing had been stored for several years. The Cq-values of Plasmodium spp., on the other hand, showed a much wider dynamic range. Abbreviation: CMV, cytomegalovirus.