Human leukocyte interferon administration to patients with symptomatic and suspected rabies

Abstract

Body fluids and brain tissue from rabid human patients have demonstrated only low titers of interferon. Therefore, pharmacokinetic studies of systemically administered and locally injected leukocyte interferon were performed in 2 North American patients with suspected rabies who showed no clinically important side effects of this therapy. Similar therapy was given to 5 patients with symptomatic rabies in Europe and America. Although no prolongation of the clinical course was seen in 3 patients given high-dose intraventricular and systemic therapy, treatment was not initiated until between 8 and 14 days after symptoms were seen. The intraventricular dosage regimen produced cerebrospinal fluid levels that appeared to fall progressively over the 24 hours after injection and demonstrated good but somewhat delayed distribution into the lumbar sac. Titers produced by this therapy were 30- to 10,000-fold higher than those normally observed in this infection, however. In the patients treated at the highest dosage, a diminished and delayed antirabies neutralizing antibody titer was observed, probably a result of the administration of the exogenous interferon.

Antemortem diagnosis and prevention of human rabies

“…Although some antiviral drugs such as ribavirine are found effective in experimental animals, they were ineffective in treating human cases. [54] Same results have been observed with Interferon[55] and high doses of intrathecally administered rabies immunoglobulin. [56] Cases of furious rabies should be isolated and sedated and allowed to depart his/her life peacefully.…”

Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review

“…There are no established antiviral treatment regimens for rabies, although various post-exposure prophylaxis schedules based on vaccine therapy with or without rabies-specific immunoglobulins are being used to prevent development of symptomatic disease. Some PK studies have been performed on the kinetics of administered anti-rabies antibodies [17, 18] and administered human interferon to support an early immune response [100]. …”

“…Pharmacokinetics of human leukocyte interferon in CSF was compared between systemic and local intraventricular direct administration [100]. This study demonstrated that interferon levels in the CSF could be maintained at potentially therapeutically active levels, also by systemic administration.…”

Management of Rabies in Humans

“…Therapy with a single agent, such as ribavirin or IFN-a, has been unsuccessful [15,16], although it is possible that a combination of specific therapies may be more effective. This approach-with the use of, for example, vidarabine and IFN-has been tried for patients with a late stage of disease [17].…”