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Molecular detection of potential alternative pathogens among MPXV-negative suspected mpox cases in Sierra Leone, 2025

Year: 2026
Type: article
Study design: Observational Study
Abstract: : Background Infectious disease outbreaks often rely on syndromic case definitions, which frequently result in "dead-end" diagnostic cases where patients meet clinical criteria but test negative for the target etiology. The 2025 Mpox epidemic in Sierra Leone highlighted a critical gap in regional surveillance: the need to identify alternative etiologies presenting with Mpox-like cutaneous manifestations. These Mpox clinical mimics can circulate simultaneously and pose significant diagnostic challenges that may hinder the effectiveness of clinical and public health interventions. Characterizing these co-circulating pathogens during an active epidemic can improve understanding of the pathogens associated with similar clinical presentations in the region and inform diagnostic strategies during outbreaks. Methods This retrospective laboratory-based surveillance study was conducted in Sierra Leone between June 16 and August 27, 2025, across eight health districts (Port Loko, Kambia, Karene, Bombali, Tonkolili, Koinadugu, Falaba, and Western Area Rural). We analyzed all clinical specimens, including lesion swabs, vaginal swabs, and crust samples previously tested negative for the monkeypox virus (MPXV) via molecular screening. Specimens were screened using multiplex PCR targeting a broad panel of pathogens, including Varicella-zoster virus, herpes simplex viruses type 1 & 2, Cytomegalovirus, Epstein-Barr virus, human herpesviruses Type 6 & 7, Haemophilus ducreyi , Treponema pallidum and Chlamydia trachomatis . Results Among the 263 MPXV-negative cases tested, at least one targeted pathogen was identified in 58.2% (153/263) of the samples. Varicella-zoster virus was the most detected pathogen identified (43.3%, n=114), alongside other significant detections including Herpes simplex virus type 2 (7.2%, n=19), Cytomegalovirus (6.8%, n=18), and Epstein-Barr virus (6.1%, n=16). Notably, the study identified several co-detections between Herpesviruses and a rare occurrence of Haemophilus ducreyi (1.1%, n=3), twice co-detected with Varicella-zoster virus. Conclusion These findings highlight the potential value of integrating multiplex differential molecular screening into Mpox outbreak surveillance to identify alternative etiologies among MPXV-negative suspected cases. Combining broader pathogen screening with clinical assessment could inform patient management and strengthen outbreak preparedness and response.
Language: English
Subfield: Virology
Open Access status: gold
Estimated APC paid: $2,770
OpenAlex ID: W7223122667
FWCI:
Cites: 37
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Related to: 10