Flavivirus cross-reactivity in serological tests and Guillain-Barré syndrome in a hematopoietic stem cell transplant patient: A case report

Abstract

Serological diagnosis of flavivirus infection is a challenge, particularly in the context of a disease associated with immune response enhancement in a transplant patient, where aspects such as previous flavivirus infections may be involved with the outcome. We report a case of a pediatric patient who developed Guillain-Barré syndrome (GBS) after matched-unrelated hematopoietic stem cell transplantation (HSCT). The patient lives in a Brazilian region that is experiencing an epidemic of Zika virus (ZIKV) and dengue virus (DENV). Because an increasing number of cases of GBS, likely triggered by ZIKV infection, are being reported in Brazil, samples from the patient were tested for both ZIKV and DENV infection. Serological assays strongly suggested a recent ZIKV infection, although infection by DENV or co-infection with both viruses cannot be ruled out. The presence of anti-DENV immunoglobulin-G in donor serum led to the hypothesis that antibodies from the donor could have enhanced the severity of the ZIKV infection. This hypothesis is in agreement with the recent findings that DENV sero-cross-reactivity drives antibody-dependent enhancement of ZIKV infection. These findings highlight the need for discussion of the indication to perform previous flavivirus tests in HSCT donors, especially in areas where ZIKV and other flaviviruses co-circulate.