Next-generation sequencing reveals viral aetiologies of encephalitis in Ghana: a prospective cross-sectional study

In Ghana, cerebrospinal fluid polymerase chain reaction (PCR) is the primary diagnostic tool for viral encephalitis. However, its application remains limited, and diagnosis is predominantly syndromic. Current data on encephalitis in Ghana are sparse and often restricted to sporadic cases, with improved PCR diagnostics elucidating some aetiological agents but leaving approximately 60% of cases undiagnosed. This diagnostic gap arises because PCR targets specific pathogens, overlooking unexpected or novel agents. Consequently, tailored patient management is hindered, patient outcomes are adversely affected, and efforts to understand the true burden of viral encephalitis are impeded. To address these challenges, we conducted a cross-sectional study at the Komfo Anokye Teaching Hospital, a major tertiary referral centre in Ghana, from May 2019 to August 2022. Forty-three (43) cerebrospinal fluid samples from suspected encephalitis patients were analysed using Polymerase chain reaction (PCR) and high-throughput next-generation sequencing (NGS) to identify a broader range of viral pathogens and assess the role of co-infections in disease outcomes. Viral encephalitis was detected in 42% (18/43) of samples, revealing 11 viruses across six families. Herpesviruses (34%) and retroviruses (28%) were the most prevalent, with human immunodeficiency virus-1 (HIV-1) and enteroviruses identified as the primary causative agents. NGS identified a broader viral spectrum, detecting 6 additional viruses (HIV-1, EBV, Mumps, HHV-6, HRV, Rotavirus A) which were not targeted by PCR. While NGS and PCR demonstrated comparable sensitivity for certain pathogens, NGS identified additional co-infections (39%, 7/18) and rare viruses. The survival rate for patients with co-infections was 28.6% (2/7), with HIV-1 and herpesviruses implicated in 85.7% (6/7) of co-infected cases. This study highlights the potential of NGS to expand the diagnostic capabilities for viral encephalitis. By overcoming the limitations of PCR, NGS provides a more comprehensive approach, enhancing our understanding of the true burden of viral encephalitis in Ghana and informing better patient management strategies.