Severe Arboviral Neuroinvasive Disease in Patients on Rituximab Therapy: A Review

Abstract

With increasing use of rituximab and other B-cell depleting monoclonal antibodies for multiple indications, infectious complications are being recognized. We summarize clinical findings of patients on rituximab with arboviral diseases identified through literature review or consultation with the Centers for Disease Control and Prevention. We identified 21 patients on recent rituximab therapy who were diagnosed with an arboviral disease caused by West Nile, tick-borne encephalitis, eastern equine encephalitis, Cache Valley, Jamestown Canyon, and Powassan viruses. All reported patients had neuroinvasive disease. The diagnosis of arboviral infection required molecular testing in 20 (95%) patients. Median illness duration was 36 days (range, 12 days–1 year) and 15/19 (79%) patients died from their illness. Patients on rituximab with arboviral disease can have a severe or prolonged course with an absence of serologic response. Patients should be counseled about mosquito and tick bite prevention when receiving rituximab and other B-cell depleting therapies.

Cache Valley virus: an emerging arbovirus of public and veterinary health importance

“…Four of the documented CVV patients were immunocompromised either because of a preexisting condition or because of treatment with immunosuppressive drugs (Wilson et al 2017, Yang et al 2018b, Baker et al 2021, Al-Heeti et al 2022). Immunosuppressive drugs, like rituximab that causes B-cell depletion in the receiving patient, have led to several severe arboviral infections, including infections with West Nile virus, tick-borne encephalitis virus, eastern equine encephalitis virus, Jamestown Canyon virus, and Powassan virus (Kapadia et al 2022). In these cases, the arboviral infection diagnosis was delayed due to atypical clinical presentation and no detectable antibody response secondary to the administration of immunosuppressive drugs in the patient.…”

“…Due to the inconsistent yearly patterns, lack of longitudinal data, and limited diagnostic reagents, there are considerable gaps in knowledge regarding CVV ecology. As human cases are likely underrecognized, it will be important to understand the risk that CVV poses moving forward (Kapadia et al 2022). More ecological longitudinal studies like those done in New York and Connecticut (Andreadis et al 2014, Dieme et al 2022a, 2022b) will help identify regionally important vectors and ideally pinpoint peak transmission periods for targeted mosquito surveillance and early detection.…”

Diagnosing viral encephalitis and emerging concepts

“…In practice, if the suspicion for HSV remains high despite an early negative result, strongly consider repeating the CSF PCR after 72 h [1]. Targeted testing of serum/CSF serologies is available for many suspected viral pathogens and is especially helpful in arboviral infections wherein initial CSF nucleic acid detection may be negative due to low viral levels [37]. In the immunosuppressed patient, nucleic acid testing may be superior to serologies for arboviral infections [37].…”

Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023

“…TBE virus occasionally has been isolated, or TBE viral RNA has been detected by nucleic acid amplification tests (NAATs), in serum, whole blood, urine, or CSF samples when a patient has neurologic illness (50,51,67,92,127,168,(183)(184)(185)(186)(187). Although these methods are insufficiently sensitive for routine diagnostic purposes, NAATs can be of value in patients who are immunocompromised (158,188,189). In addition, if testing is done during the initial febrile (viremic) phase of illness before neurologic symptoms develop and antibodies are measurable, RNA often can be detected; however, patients usually only are tested after neurologic disease manifests (49,169,184).…”