Extrahepatic hepatitis E virus in cerebrospinal fluid of people living with human immunodeficiency virus at an Academic Hospital, South Africa

BACKGROUND: Hepatitis E virus (HEV) continues to cause global health problems and has the potential to cause extrahepatic manifestations. This study aimed to investigate extrahepatic HEV in stored cerebrospinal fluid (CSF) from people living with HIV (PLWHIV). METHODS: In this cross-sectional study, 54 CSF specimen samples of PLWHIV and past medical history of neurologic disorders were screened for HEV at an academic hospital in South Africa. CSF specimens were subjected to ribonucleic acid (RNA) isolation and in-house polymerase chain reaction (PCR) amplification. HEV amplicons were sequenced for genotyping and descriptive statistical analysis was used to analyze the study data. RESULTS: All 54 CSF samples came from the Black African ethnic group. PCR amplification of HEV RNA was successful in 61% (33 of 54) of the samples, with 52% (17 of 33) being from females. No statistical significance variations were observed for sex (P = 0.7) between HEV RNA-positive and -negative samples. The median age was 34 years (interquartile range [IQR]: 21, 28-49), with no statistical significance variation in age group (P = 0.7). The median for the cluster of differentiation 4+ T-cell count was 306 cells/µL (IQR: 476, 62-538), with 127 cells/µL (IQR: 31-465) among the 13 HEV RNA-positive and 436 (IQR: 244-664) among 20 HEV-negative samples and with no significant statistical variation (P = 0.087). A total of 11 nucleotide sequences demonstrated similarity to HEV genotype 3 (HEV Gt-3), previously isolated from swine in Canada, Italy, and Japan, as well as from humans in Japan, Switzerland, and France. CONCLUSIONS: To the best of our knowledge, this is the first study to report extrahepatic HEV in the CSF of PLWHIV in South Africa, with a past clinical history of neurologic symptoms. The findings give preliminary evidence and knowledge of circulating HEV genotype 3 with possible zoonotic transmission in our region, necessitating the enhanced molecular screening to improve diagnosis and management of HEV.