Experimental Drug Treatment for Clinical Rabies
No experimental drug or drug combination has demonstrated reliable survival benefit for clinical rabies, and the disease remains virtually 100% fatal once symptoms develop. The only documented survivors (6 total) either received rabies vaccination before symptom onset (5 patients) or survived through an unproven experimental protocol that has since failed in all subsequent attempts 1, 2.
Current Evidence on Experimental Therapies
Historical Experimental Approaches
The Advisory Committee on Immunization Practices (ACIP) has documented multiple failed experimental interventions, including 3:
- Vidarabine
- Multisite intradermal vaccination with cell-culture vaccines
- Human leukocyte interferon
- Rabies immune globulin (intravenous and intrathecal routes)
- Antithymocyte globulin
- Inosine pranobex
- Ribavirin
- Ketamine
- High-dose steroids
None of these approaches have proven effective, and initiating rabies vaccination after symptom onset is not recommended and may be detrimental 3.
Recent Experimental Drug Combinations
Animal Model Studies (Not Proven in Humans)
The most recent experimental evidence comes from murine models showing modest survival extension with combination therapy 4:
- Drug cocktail components: T-705 (favipiravir), ribavirin, interferon α/β, caspase-1 inhibitor, TNF-α inhibitor, MAPKs inhibitor, and human rabies immune globulin
- Result: Statistically significant extension of survival time (p = 0.0312) but not cure
- Key finding: Interferon α/β showed the most significant impact on survival among the tested agents 4
A similar 2019 study demonstrated that combination treatment initiated at day 4 post-infection resulted in increased survival time and lower viral RNA in brain and spinal cord, but again, no cures 5.
Critical Limitations of Experimental Approaches
The Milwaukee Protocol has been definitively proven ineffective and should no longer be used 6, 7. This protocol, which included therapeutic coma with ketamine, has failed in virtually all subsequent attempts after the single unvaccinated survivor 7.
Current expert consensus indicates 6, 8:
- Ribavirin and interferon-α: Disappointing results in human cases
- Ketamine and amantadine: Insufficient evidence to support continued use
- Minocycline and corticosteroids: Should NOT be used due to concerns about disease aggravation 6, 8
Clinical Recommendations
When to Consider Experimental Therapy
Medical staff at specialized tertiary care hospitals might consider aggressive experimental therapies only in 1:
- Confirmed rabies cases
- Young, healthy persons
- Early stage of clinical disease
- After in-depth discussions and informed consent
Critical Counseling Points
Families must understand 1:
- High probability of treatment failure (essentially 100% mortality)
- Anticipated significant expenses
- Rare survivors may have serious neurological sequelae requiring lengthy rehabilitation
Standard of Care Approach
The recommended approach focuses on comfort care and adequate sedation in an appropriate medical facility 1, 2. This is necessary because patients become extremely agitated with stimuli such as loud noises, air currents, and running water during the acute neurologic phase 1, 2.
Prevention Remains the Only Effective Strategy
Postexposure prophylaxis combining wound treatment, local infiltration of rabies immune globulin, and vaccination is uniformly effective when appropriately administered before symptom onset 1. This represents the only proven life-saving intervention for rabies.
Common Pitfalls to Avoid
- Do not delay or withhold postexposure prophylaxis in exposed individuals hoping for experimental treatment options
- Do not use the Milwaukee Protocol or therapeutic coma approaches
- Do not administer corticosteroids, which may worsen outcomes 6, 8
- Do not initiate rabies vaccination after clinical symptoms develop 3