Persistent viral shedding after acute Lassa fever: thorough evidence arouses more noteworthy concerns

Abstract

With great interest, we have read the study by Anke Thielebein and colleagues,1Thielebein A Ighodalo Y Taju A et al.Virus persistence after recovery from acute Lassa fever in Nigeria: a 2-year interim analysis of a prospective longitudinal cohort study.Lancet Microbe. 2022; 3: e32-e40Summary Full Text Full Text PDF PubMed Google Scholar which found evidence of post-infection Lassa virus shedding in body fluids, including seminal fluid, in a prospective, longitudinal cohort. The results of this study are quite instructive for individuals who have recovered from acute Lassa fever, offering practicable suggestions for the risk period by recommending the adoption of safe sex practices. Previous studies on Zika virus and Ebola virus have explained the potential of sexual transmission for these acute infection-causing viruses, and subsequent mechanism studies have provided new insights for virus replication and clearance dynamics. However, due to the rarity of Lassa fever, no cases of sexually transmitted disease have been reported so far. Zika virus usually invades the cerebrum and can pass through the blood–testis barrier. However, the main target of Ebola virus and Lassa virus is the endothelium, and host immunity towards these two types of viral infection varies. More than half of patients infected with Lassa virus have either IgG or IgM antibodies and neither are associated with recovery;2Johnson KM McCormick JB Webb PA Smith ES Elliott LH King IJ Clinical virology of Lassa fever in hospitalized patients.J Infect Dis. 1987; 155: 456-464Crossref PubMed Google Scholar by comparison, the early antibody response is a pivotal factor influencing disease outcomes for Ebola virus.3Baize S Leroy EM Georges-Courbot MC et al.Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients.Nat Med. 1999; 5: 423-426Crossref PubMed Scopus (452) Google Scholar In addition, T-cell responses are transient in patients with Lassa fever,4Baize S Marianneau P Loth P et al.Early and strong immune responses are associated with control of viral replication and recovery in Lassa virus-infected cynomolgus monkeys.J Virol. 2009; 83: 5890-5903Crossref PubMed Scopus (131) Google Scholar which indicates that severe Lassa fever is associated with immunosuppression. Thielebein and colleagues1Thielebein A Ighodalo Y Taju A et al.Virus persistence after recovery from acute Lassa fever in Nigeria: a 2-year interim analysis of a prospective longitudinal cohort study.Lancet Microbe. 2022; 3: e32-e40Summary Full Text Full Text PDF PubMed Google Scholar scored disease severity on the basis of six clinical chemistry parameters. It would be beneficial to assess whether prolonged shedding of Lassa virus in seminal fluid correlates with specific impaired T-cell responses, especially if impared immunity responses lead to a higher likelihood of isolating the virus, considering that early T-cell responses correlate with survival in Lassa virus-infected non-human primates.4Baize S Marianneau P Loth P et al.Early and strong immune responses are associated with control of viral replication and recovery in Lassa virus-infected cynomolgus monkeys.J Virol. 2009; 83: 5890-5903Crossref PubMed Scopus (131) Google Scholar Moreover, whether the prolonged shedding of the virus is a factor that leads to relapse of infection is unknown and of great concern, as Ebola relapse has been identified in some patients and non-human primates who were treated with convalescent plasma or experimental antibodies.5Mbala-Kingebeni P Pratt C Mutafali-Ruffin M et al.Ebola virus transmission initiated by relapse of systemic Ebola virus disease.N Engl J Med. 2021; 384: 1240-1247Crossref PubMed Scopus (21) Google Scholar Similar phenomena have been identified in Junín virus (the causative agent of Argentine haemorrhagic fever), and Machupo virus (the agent of Bolivian haemorrhagic fever).5Mbala-Kingebeni P Pratt C Mutafali-Ruffin M et al.Ebola virus transmission initiated by relapse of systemic Ebola virus disease.N Engl J Med. 2021; 384: 1240-1247Crossref PubMed Scopus (21) Google Scholar Therefore, we hope that future studies will evaluate virus shedding along with immunological factors, which might help to reveal the pathogenesis of this deadly illness. We declare no competing interests. Virus persistence after recovery from acute Lassa fever in Nigeria: a 2-year interim analysis of a prospective longitudinal cohort studyLassa virus RNA is shed in various body fluids after recovery from acute disease. The persistence of infectious virus in seminal fluid implies a risk of sexual transmission of Lassa fever. Full-Text PDF Open Access