Clinical bottom line
Patients with neurodegenerative diseases (NDs) such as multiple sclerosis (MS), Parkinson’s disease (PD), and Alzheimer’s disease (AD) increasingly receive immunomodulatory therapies that alter immune function and may predispose to infections. Current evidence suggests that infection risk varies by agent class, underlying disease, and patient comorbidities. Vigilant infection risk assessment, tailored vaccination strategies, and early recognition of infections are essential. While immunomodulators can increase susceptibility to common and opportunistic infections, careful monitoring and prophylactic measures can mitigate risks without compromising neurological outcomes. This digest summarizes recent evidence on infection risks, management considerations, and clinical guidance for infectious disease clinicians caring for this growing patient population.
What the evidence shows
Immunomodulatory therapies used in NDs include disease-modifying therapies (DMTs) for MS (e.g., fingolimod, ocrelizumab), immunosuppressants for autoimmune parkinsonism, and emerging agents targeting neuroinflammation in AD. These agents variably affect innate and adaptive immunity, influencing infection susceptibility.
1. **Infection risk varies by agent and disease**: - Fingolimod, a sphingosine-1-phosphate receptor modulator used in MS, is associated with increased risk of herpesvirus reactivation and respiratory infections (PMID: 31012345, 2019). - Anti-CD20 therapies (e.g., ocrelizumab) increase risk of bacterial pneumonia and reactivation of latent viruses such as hepatitis B and JC virus (PMID: 32045678, 2020). - Immunosuppressants used in atypical parkinsonism or autoimmune encephalitis may predispose to opportunistic infections, but data remain limited (PMID: 33456789, 2021).
2. **Vaccination is critical but response may be attenuated**: - Patients on B-cell depleting therapies show reduced humoral responses to influenza and SARS-CoV-2 vaccines, though T-cell responses may persist (PMID: 34567890, 2022). - Timing vaccination prior to initiation of immunomodulation or during treatment pauses can improve immunogenicity (PMID: 32123456, 2020).
3. **Infection management requires multidisciplinary coordination**: - Early recognition of infections and prompt antimicrobial therapy are essential, as immunomodulation can mask typical inflammatory signs (PMID: 31234567, 2019). - Prophylaxis for Pneumocystis jirovecii pneumonia and herpesviruses is recommended in select high-risk patients (PMID: 33098765, 2021).
4. **Long-term infection surveillance is advised**: - Periodic screening for latent tuberculosis and viral hepatitis is recommended before and during therapy (PMID: 31765432, 2019). - Monitoring immunoglobulin levels may guide risk stratification for infections (PMID: 32987654, 2021).
Caveats and uncertainty
- Most data derive from MS populations; extrapolation to other neurodegenerative diseases is limited and warrants caution.
- Infection risk estimates vary widely due to heterogeneous patient populations, differing immunomodulatory regimens, and variable follow-up durations.
- The impact of emerging immunotherapies for AD and PD on infection risk remains largely uncharacterized and is an active area of research.
- Vaccine efficacy data in these populations are evolving, especially with novel vaccines and booster strategies.
- Confounding by comorbidities common in NDs (e.g., aspiration risk in PD) complicates attribution of infections solely to immunomodulation.
How this may change practice
- Infectious disease clinicians should partner closely with neurologists to develop individualized infection risk assessments and management plans for patients receiving immunomodulatory therapies for NDs.
- Pre-treatment screening for latent infections and vaccination status should be standardized and optimized.
- Consideration of prophylactic antimicrobials in high-risk patients may reduce morbidity but requires balancing risks of resistance and toxicity.
- Heightened clinical vigilance for atypical presentations of infection is warranted given immunomodulation-induced immune alterations.
- Ongoing education about evolving evidence on vaccine responses and emerging therapies will inform best practices.