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Sherrilyn and Ken Fisher Professor of Medicine
Division of Infectious Diseases
Johns Hopkins University School of Medicine
Dr Auwaerter: consulting fees: EMD Serono, Verily; contracted research: Humanigen; other financial or material support: Johnson & Johnson.
Immunization Is Still of Primary Importance
The first key point that I want to make on influenza prevention strategies in the immunosuppressed population is that health care providers should continue to ensure that patients are immunized even if they do not have confidence that the patient will have a robust immune response to the vaccine. There may still be some protection afforded in these populations, perhaps not by antibody generation but by T-cell-based immunity. Many providers understandably feel that immunization is not worth the effort if the patient is on a drug like rituximab or has severe B-cell depletion syndrome. However, I believe immunization is still warranted in most circumstances and when feasible, the appropriate timing of vaccinations to maximize their effectiveness is the best strategy.
Timely Post-Exposure Chemoprophylaxis: An Effective Strategy
Severely immunosuppressed individuals should be considered for post-exposure chemoprophylaxis if an influenza infection occurs in a household member or close contact. Optimally, we would like to initiate the antiviral within 48 to 72 hours of exposure. Influenza virus tends to be acquired and start productive illness in as little as 24-48 hours, faster than SARS-CoV-2 that has a more gradual onset, typically in the 5-7 day range.
There are several strategies for chemoprophylaxis, and oral therapy is generally the easiest. Ten days of the neuraminidase inhibitor oseltamivir is one approach and it has the most data and experience behind it. Recently, Ikematsu and colleagues showed that a single, oral dose of baloxavir was an effective postexposure prophylactic in a randomized, placebo-controlled trial, with 1.9% of patients developing clinical influenza in the baloxavir arm compared to 13.6% in the placebo arm (aRR: 0.14 [95% CI: 0.06-0.30]; P <.001). The obvious advantage with baloxavir is that it is a “fire and forget” strategy for your at-risk patients. This may be an excellent option for adolescents or other individuals for whom compliance is expected to be an issue.
The Flip Side: What About Resistance?
There is tension regarding concerns of overuse of influenza chemoprophylaxis and the promotion of antiviral resistance. The CDC does not highly recommend this strategy outside of institutional outbreaks except in very specific populations. During the 2007-2008 influenza season, many circulating strains of influenza A were oseltamivir-resistant, providing the impetus for much of this concern. Oddly enough, despite the continued use of oseltamivir, significant rates of resistance to the drug have not been documented—even in areas of substantial use like Japan. This resistance behavior remains unexplained.
Consequently, I have become a little less hesitant to employ this strategy for the present but have a renewed alertness. As an infectious disease physician, I don’t particularly appreciate overusing drugs, but if there are patients at risk for severe influenza who are not immunized, even if they are not severely immunosuppressed but have risk factors for severe influenza, I will at least inquire whether they may want to take chemoprophylaxis because the attack rates are 5% to 20%. I must add the caveat that this is not the official CDC guidance on this subject.
Some Final Points on Preventative Strategies
Timely use of antivirals after exposure to infected household contacts is crucial for preventing subsequent infections in highly immunosuppressed individuals. Although not yet clinically supported by research, a potential advantage of using baloxavir is that it reduces viral shedding faster than oseltamivir, limiting the time of infectivity. On the other hand, when considering baloxavir for chemoprophylaxis, there are higher rates of virus shed with mutations as a natural consequence of inhibiting the viral RNA polymerase. Hence, I would not use baloxavir widely or in multiple individuals in one household.
Another strategy for individuals at high risk of influenza complications is to arrange for early empiric therapy. I typically only do this when someone is traveling, particularly if they are going abroad. When people are local, I prefer to allow them to call at the onset of symptoms as I would rather discuss than have people self-starting.