LAUSR

Dear Editor, We read with great interest the study by Ting Shi et al. in a recent issue of the Journal of Medical Virology where they suggested that plasma Epstein‐Barr Virus (EBV) DNA detection has great diagnostic value for infectious mononucleosis (IM). However, EBV‐specific antibodies and peripheral lymphocyte tests are more suitable as concomitant tests to the diagnosis of IM as they have different sensitivities in different age stages and course of disease. Also, some similar studies have demonstrated that reliance on EBV‐specific antibodies alone may significantly underestimate the diagnosis of IM. Positive plasma EBV DNA (viremia) is an important indicator of virus replication with high sensitivity and specificity for the diagnosis of IM which has attracted much attention recently. However, a large‐scale clinical trial showed that some patients with IM still had negative plasma EBV DNA findings. The reason for the unexpected results is that cell‐free EBV DNA is not limited to plasma, it can be found in other sterile specimens such as cerebrospinal fluid, bone marrow, pleural fluid, sterile surgical biopsy tissue, and so forth. An interesting study was carried out to investigate the efficacy of multianatomical site EBV DNA testing in patients with IM in our center since 2015. The first case (3‐year‐old female) presented with fever, cervical lymphadenitis, pharyngotonsillitis, and hepatosplenomegaly. Repeated blood testing showed a white blood cell count of 4.06–5.4 × 10/L and a lymphocyte count of 2.04–3.62 × 10/L, and no atypical lymphocytes were found. EBV‐specific antibodies suggested a typically primary infection: the presence of virus capsid antigen (VCA) immunoglobulin M (IgM) and VCA immunoglobulin G (IgG) without nuclear antigen (NA) IgG. We tried multianatomical site EBV DNA testing in this patient. The plasma EBV DNA testing showed a positive result (9.08 × 10 copies/ml). We were surprised to find that EBV DNA both in bone marrow (4.34 × 10 copies/ml) and cerebrospinal fluid (2.83 × 10 copies/ml) was also positive. However, repeated plasma EBV DNA testing revealed a rapid decline to negative on the 18th day. In contrast, cerebrospinal fluid EBV DNA remained positive until the 165th day. The second case (9‐year‐ old female) presented with fever, periorbital edema, pharyngotonsillitis, and cervical lymphadenitis. Blood tests indicated a normal white blood cell range (4.47–11.23 × 10/L) and a lack of lymphocytosis (2.31–4.05 × 10/L). EBV‐specific antibodies of this patient also showed a typical primary infection (VCA‐IgM[+] VCA‐ IgG[+] NA‐IgG[−]). EBV DNA was undetectable in plasma, but a high viral load (2.26 × 10 copies/ml) was found in the cerebrospinal fluid. These two cases showed us that multianatomical site EBV DNA testing could increase the sensitivity of diagnosis. EBV DNA may be present at other anatomical sites even when plasma EBV DNA turns negative. It could be suitable to try testing for other sterile specimens when plasma EBV DNA is undetectable. To confirm our findings, we will conduct a more systematic study in the future, including a greater number of cases. IM is common in children and can be diagnosed based on plasma EBV DNA and EBV‐specific antibody levels in most patients. Multianatomical site EBV DNA testing could help in the diagnosis of IM and its associated complications, especially for patients with difficulty in diagnosis.