Infection Of Imjin Virus Or SFTS Virus In Healthy Humans And Clinical Diagnosed Hemorrhagic Fever With Renal Syndrome Patients

Imjin virus(MJNV)is a newly discovered shrew-borne Hantavirus.The pathogenicity of MJNV to humans is unknown.The aim of this study is to investigate whether MJNV could infect humans.Partial MJNV nucleocapsid protein(NP)was cloned and expressed in Escherichia coli.The purified recombinant NP was used as antigen for double-antigen sandwich ELISA,IgM capture ELISA and Dot blot to detect MJNV specific antibody in 227 hemorrhagic fever with renal syndrome(HFRS)patients and 385 healthy persons' sera from Qingdao City,Shandong Province,China.The specificity and cross-reaction of the partial MJNV NP were evaluated by reaction with 90 healthy persons' sera obtained from non-endemic areas of MJNV and100 Hantaan or Seoul virus antibodies positive HFRS patients' sera of the 227 HFRS sera.None of these sera reacted with the MJNV NP,indicating that the MJNV NP had no cross-reaction with human normal sera and Hantaan or Seoul viral antibody.In the testing of healthy humans from epidemic areas,two of 385 healthy persons were positive to MJNV IgG antibody,suggesting MJNV infected humans.We demonstrated that MJNV could infect humans and the information is of concern to public health about the potential of MJNV to cause emerging infectious disease in humans.In the testing of 127 sera of HFRS-causing virus-negative HFRS patients and none of these patients were positive to MJNV.As severe fever with thrombocytopenia syndrome(SFTS)was prevalent in the study areas and SFTS had similar clinical manifestations and epidemic characters(such as spatial and temporal distributions)with hemorrhagic fever with renal syndrome(HFRS),we then tested the SFTS virus in these hantaviruses-negative HFRS patients to determine whether SFTS could be clinically misdiagnosed as HFRS.Among the 55 hantaviruses-negative patients' sera with sufficient volume for testing,four(7.3%)were IgM antibody positive to SFTSV.The results indicated that SFTS patients could be clinically misdiagnosed as HFRS.The misdiagnosed SFTS patients had clinical manifestations similar to HFRS and were hardly to be differentiated from HFRS clinically.Knowledge of salient features associated with HFRS may help healthcare providers in diagnosis.The sample size of SFTS was 4 and we could not expect the 4 cases would be statistical significant to compare the differences between HFRS and SFTS.To better differentiate SFTS from HFRS,we further estimated pooled proportions of the clinical manifestations and laboratory findings of SFTS and HFRS from previous studies by Meta-analyses as supporting information.The Meta-analyses included 3,200 cases of HFRS and 5,046 cases of SFTS respectively,which could make up for the small size of comparison.The results showed that the following manifestations including skin flushing(facial flushing,neck flushing,and chest flushing),oliguria,periorbital pain,periorbital edema,hypotesion,and/or icterus only presented in HFRS,while swollen lymph nodes and expectoration are only present in SFTS.But unfortunately these symptoms and signs may not always presents in SFTS or HFRS patients,respectively.The misdiagnosis of SFTS as HFRS causes particular concern because it may increase the risk of death of SFTS patients and person to person transmission of SFTSV without proper care for SFTS patients.To avoid misdiagnosis,rapidly and reliable diagnostic approaches like ELISA should be widely applied in the clinical settings.