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.

Comparison of Four Serological Methods and Two Reverse Transcription-PCR Assays for Diagnosis and Surveillance of Zika Virus Infection

“…Since the introduction of ZIKV into the Americas in 2015, accurately differentiating ZIKV and DENV infections has been a challenge. Serological cross-reactivity among flaviviruses (8,10,11,13) and the low ZIKV viral load and short period of detectable viremia (32,33) have complicated serological diagnosis and molecular diagnosis, respectively. Hence, it is necessary to thoroughly evaluate multiple diagnostic assays.…”

“…The cocirculation of several arboviruses in the Americas that cause similar symptoms and display antibody cross-reactivity poses a challenge for diagnosis and surveillance (10)(11)(12)(13)(14). In particular, detection and differentiation of the antigenically related flaviviruses dengue virus (DENV) and ZIKV have relied to date mostly upon molecular methods (15)(16)(17).…”

Flavivirus cross‐reactivity, Guillain‐Barré syndrome, and hematopoietic stem cell transplant patient: A comment

“…To the Editor The case report by Raboni et al 1 In addition, the concurrent observation on DENV and ZIKV immunoreactive cases are reported from many tropical countries, including to our setting in tropical Indochina. 2 Of interest, in our setting, there is no observation that the co-presentation of many arbovirus antibodies contributes to an increased severity of any infected cases.…”

Understanding Flavivirus Capsid Protein Functions: The Tip of the Iceberg

“…ADE occurs when antibodies circulating from a previous infection bind new antigen without neutralizing virus, resulting in a more efficient uptake into monocytes. This is common across the dengue serotypes and extends to Zika virus as well [95,96]. Therefore, there may also be promise in a subunit vaccine containing a viral antigen, such as soluble capsid protein.…”