The Risks of Ticks and Mosquitoes for Patients on Rituximab

Know the risks of vector-borne diseases when prescribing immunosuppressive drugs and educate your patients about ways to prevent tick and mosquito bites.

Ticks, Mosquitoes, and Patients on Rituximab: 5 Things to Know

As the weather heats up, counsel your patients about diseases associated with mosquito and tick bites, particularly patients taking immunosuppressive drugs such as rituximab or other B cell– depleting immunotherapies. These drugs are often prescribed for oncologic, rheumatologic, and neurologic conditions and can help improve patients' quality of life. However, they can also put patients at risk for severe disease from mosquito- and tickborne viruses.

Here are five things to know about prescribing this class of drugs and counseling your patients about how to prevent arboviral infections like West Nile virus.

1. Patients on B cell–depleting immunotherapies are at high risk for severe disease from arboviral infection.

A recent case series of 21 patients on rituximab who were diagnosed with arboviral disease found that all patients had neuroinvasive disease, including encephalitis or acute flaccid myelitis. Fifteen of 19 (79%) patients whose outcome was reported died from complications of their arboviral disease. Those who survived often had long-term disabilities like cognitive and motor dysfunction.

B cell–depleting immunotherapies such as rituximab and ocrelizumab are effective therapies for many oncologic, rheumatologic, and neurologic conditions, but they can also place patients at risk for severe infectious diseases because of the profound B-cell depletion resulting from these therapies.

Although various treatments have been evaluated for West Nile virus disease, there are no known effective treatments for any arboviral disease. Clinical management of disease symptoms is supportive. Decreasing or stopping immunosuppressive medications, if possible, might help patients develop an immune response to control the virus. However, it can take as long as 12 months for B cells to return to normal after stopping rituximab.

2. Patients on B cell–depleting immunotherapies often have atypical signs and symptoms of arboviral disease.

Patients on rituximab reported in the case series often had an atypical and prolonged course of disease with higher fatality than usual. Most arboviral infections in healthy patients are asymptomatic or present as a nonspecific febrile illness. Even for the small proportion of people who develop neuroinvasive disease, fatality ranges from 10% to 30%, compared with 79% in the case series.

Antibodies and B cells play a critical role in preventing and limiting the neurologic spread of West Nile virus. Depletion of B cells can result in prolonged viral replication, for weeks or even months. This can prolong the course of disease and result in atypical clinical characteristics. For example, patients might present with illness outside of the typical mosquito and tick season (usually April through October) or have a more indolent clinical course with lack of inflammation on imaging or in cerebrospinal fluid. Therefore, even if mosquitoes and ticks are not active, consider arboviral diseases in the differential for patients on B cell–depleting immunotherapies who present with fever or neurologic symptoms.

3. Prioritize molecular testing if you suspect an arboviral disease in patients on B cell–depleting immunotherapies.

Timely diagnosis of an arboviral infection in patients helps guide clinical management and treatment decisions (eg, avoiding unnecessary procedures and antibiotics). Diagnosing and reporting of arboviral diseases to state and local health departments can help public health authorities respond and prevent additional cases.

Testing for most domestic arboviral infections is done through serologic (antibody) tests. However, patients on B cell–depleting immunotherapies often do not generate a detectable antibody response, which can lead to false-negative results. In the case series, 20 patients underwent initial serologic testing and 19 had negative results. If you suspect that a patient on rituximab or a similar drug might have an arboviral disease, prioritize molecular testing (eg, RT-PCR) to detect whether viral RNA is present in serum, cerebrospinal fluid, and/or tissue specimens.

Although RT-PCR testing is available for West Nile virus at many commercial and public health laboratories, it is not as readily available for other domestic arboviruses (eg, Powassan, St. Louis encephalitis, Eastern equine encephalitis). This testing can be performed at some state public health, CDC, or other diagnostic reference laboratories. Contact your state or local public health department to request specialized testing.

4. Understand the global impact of arboviruses.

If you prescribe rituximab and similar B cell–depleting immunotherapies, it is especially important to be aware of the epidemiology and global distribution of arboviral diseases and counsel your patients on preventing mosquito and tick bites in areas where they live and during travel.

West Nile virus is the most common domestic arbovirus in the continental United States and is distributed throughout many other parts of the world. Other arboviruses, such as Powassan virus, Eastern equine encephalitis virus, and La Crosse virus, cause focal and sporadic disease cases and outbreaks in certain US regions. Dengue, Zika, chikungunya, yellow fever, and tick-borne encephalitis viruses are examples of viruses that are usually found outside of the continental United States.

You can find more information on state and local health department websites or CDC websites.

5. Counsel your patients on preventing mosquito and tick bites.

Talk to your patients about preventing mosquito and tick bites by using personal protective measures, especially patients who are on B cell–depleting immunotherapies like rituximab. While these drugs can greatly improve the quality of life for patients suffering from various conditions, it is important to communicate the associated risks.