CDC warns of severe arboviral disease risk with B cell-depleting therapies

Clinical takeaway: Counsel patients receiving B cell-depleting or B cell-modulating therapies about stringent mosquito and tick bite prevention, and use molecular testing (RT-PCR or mNGS) rather than relying on serology when arboviral infection is suspected.

In a new Health Advisory, CDC warns that patients treated with B cell-depleting or B cell-modulating medications, particularly anti-CD20 monoclonal antibodies (eg, rituximab, ocrelizumab, ofatumumab, obinutuzumab, ublituximab), face an increased risk of severe arboviral neuroinvasive disease. Concern is heightened by the strong early start to the 2026 West Nile virus season and the continued risk of mosquito- and tick-borne viral transmission across the US.

Most arboviral infections are asymptomatic, but immunocompromised patients may develop severe neurologic disease, including meningitis, encephalitis, or acute flaccid myelitis. Published reports of arboviral neuroinvasive disease in patients receiving anti-CD20 therapies have shown an approximately 40% mortality rate, with many survivors experiencing long-term neurologic sequelae. West Nile virus has been the most frequently reported pathogen, although Powassan, eastern equine encephalitis, Jamestown Canyon, La Crosse, Cache Valley, and Potosi viruses have also been implicated. Rare cases of chronic, progressive viral encephalitis lasting months to years have been reported in rituximab-treated patients and were uniformly fatal.

The advisory has important implications for pharmacotherapy management. Clinicians prescribing or monitoring anti-CD20 agents, anti-CD38 therapies, or other B cell-targeted immunomodulators should discuss arboviral infection risk as part of routine counseling and reinforce preventive measures, including EPA-registered insect repellents, permethrin-treated clothing, and avoidance of mosquito- and tick-exposed environments.

Because B cell-targeted therapies can impair antibody production, infected patients may have prolonged viremia and absent or delayed antibody responses, making conventional IgM serology less reliable. For patients receiving these therapies who present with unexplained fever or neurologic symptoms, CDC recommends obtaining a detailed exposure and travel history and prioritizing molecular diagnostic testing, including RT-PCR or metagenomic next-generation sequencing. Consultation with state or local health departments may help determine optimal specimen collection and testing strategies.

There are currently no approved vaccines, prophylactic agents, or antiviral treatments for arboviral diseases endemic to the US, underscoring the importance of prevention and early recognition in high-risk patients.

Source: Centers for Disease Control and Prevention (CDC). (2026 Aug 11) Health Alert Network (HAN). Risk of Severe Arboviral Disease in Patients Receiving B Cell-Depleting or Modulating Medications