Prophylactic Therapy of Japanese Encephalitis Passive Immunization Combined with CO 2 Inhalation. ∗

Abstract

Discussion and Summary

Combined treatment with AB followed by exposure to CO₂ protected a significant proportion of mice against lethal infection with JEV when treatment was started on the 4th day after inoculation, before disease was evident. (Variance ratio by analysis of variance for AB-CO₂ treated mice vs untreated controls greater than 0.01%.) AB alone was much less effective. We have not shown that the passage of AB into CNS tissue was increased by CO₂ treatment but this is the most reasonable explanation of our results in view of the adverse effect of CO₂, and the limited protection by AB alone. When the first treatment was delayed until the fifth or sixth day, there was no protection and most patients with JE are not seen by physicians until one or more days after onset of encephalitis. Thus effective therapy of human JE by this method is not promising.

On the other hand the experimental test was very rigorous. Intranasal inoculation of JEV is probably followed by invasion of the CNS via the olfactory nerve producing a generalized encephalitis before an effective AB response occurs. In human infection which is usually inapparent, the introduction of virus into the skin is followed by proliferation of virus outside of the CNS but is rarely followed by CNS disease(10). More than half of those who do develop encephalitis recover. A significant factor in resistance to CNS invasion and in recovery after encephalitis is thought to be specific AB response. If so, administration of AB followed by exposure to CO₂ would augment the natural immune response and might be more effective in the human than in the experimental disease. That some AB treated mice did recover after development of CNS symptoms indicates that the precarious balance between host and parasite can be influenced favorably even when the CNS is invaded. Further experimental study of combined CO₂ AB therapy with an experimental disease more like human arbor-virus encephalitis is desirable.