Etiologies of community-acquired febrile illness identified by TaqMan Array Card qPCR on blood samples: a systematic...

Community-acquired febrile illness presents a significant diagnostic challenge. The TaqMan Array Card (TAC) enables simultaneous detection of many bacterial, viral, parasitic, and fungal pathogens. This systematic review aimed to characterize the etiologies of community-acquired fever diagnosed by TAC directly on blood specimens. A systematic search of PubMed, Scopus, Embase, and Web of Science (from inception to January 2026 in English) identified studies using TAC to detect pathogens directly in human blood to identify the etiology of community-acquired febrile illness. Eligible studies were appraised using a modified Joanna Briggs Institute (JBI) checklist. Pooled proportions and meta-analyses were conducted using a random-effects model. A total of 16 studies comprising 8,937 participants from 12 African and Asian countries met inclusion criteria. TAC detected at least 1 pathogen in 0.43 (95% CI [0.32; 0.54]), with high between-study heterogeneity (I² = 99%). Parasitic infections were most common (56%), nearly all due to Plasmodium spp., followed by bacterial (26%), viral (22%), and fungal (0.5%) etiologies. Plasmodium spp., Rickettsia spp., dengue virus, Lassa fever virus, Streptococcus pneumoniae, Orientia tsutsugamushi, Mycobacterium tuberculosis complex, and Salmonella spp. were the most frequently identified pathogens. Culture-negative bacteria accounted for 56% of bacterial detections. Positivity with more than 1 organism occurred in 6% of cases. TAC showed strong concordance with blood culture for culturable organisms (positive agreement: 73%, 95%CI [0.53; 0.89]; negative: 98%, 95%CI [0.95; 1.00]). TAC provides culture-independent pathogen detection and reveals overlooked causes of febrile illness, such as culture-negative bacteria. Its application may improve clinical diagnosis and surveillance programs.

Accurate identification of the causes of community-acquired febrile illness is essential for guiding clinical decision-making, surveillance programs, and public health response. This systematic review and meta-analysis synthesizes data from more than 8,937 patients across Africa and Asia tested with blood-based TaqMan Array Card (TAC) assays. TAC enabled broad, culture-independent detection of bacterial, viral, parasitic, and fungal pathogens-revealing both expected causes, such as Plasmodium spp. and dengue virus, and neglected culture-negative bacteria including Orientia tsutsugamushi, Coxiella burnetii, and Rickettsia spp. By uncovering these underrecognized etiologies, TAC provides valuable pathogen-level data to strengthen fever surveillance, inform outbreak detection, and refine regional disease prioritization frameworks. These findings highlight the potential of high-throughput molecular diagnostics to enhance infectious disease control, particularly in resource-limited settings.