Study suggests antibiotic may prevent dreaded brain fever

February 19, 2008

Two researchers from National Brain Research Center (NBRC) suggest that a common antibiotic called minocycline may prevent children from death due to Japanese encephalitis (JE), or commonly known as brain fever. Japanese Encephalitis virus is the causative agent for JE. Although there is no consolidated official figure for JE cases in India, a rough estimate would indicate a few thousands fatalities every year.

The team found that minocycline, an USFDA approved drug, often used to treat acne, limits the death by reducing the microglial activation, neuronal death as well as viral replication. Microglia are cells that act as the "cleanup crew" for the Central Nervous System (CNS). They destroy damaged cells by releasing toxins and engulfing them. Should they become activated and release their toxins in the CNS, the toxins will kill the healthy neurons critical for normal function of brain.

“Our studies in mice suggest that this antibiotic may be a strong candidate for further consideration as a therapeutic drug in patients with JE” said Anirban Basu, PhD, Staff Scientist and senior author of this work from NBRC, Manesar, Haryana. The study titled “Minocycline neuroprotects, reduces microglial activation, inhibits caspase-3 induction, and viral replication following Japanese Encephalitis” will be published in the future issue of Journal of Neurochemistry, a journal of the International Society for Neurochemistry.

Previous studies from the same group have shown that following JE there was an increased production of cytokines, proteins that cause inflammation of the brain as well as death of neurons. This study goes a step further to show that minocycline is helpful in reducing the level of cytokines and neuronal death following JE. The major finding in this study is that treatment with minocycline provides a complete protection against experimental JE. Minocycline’s neuroprotective action is associated with marked decrease in 1) neuronal death, 2) microgliosis and production of cytokine and 3) viral titre. Furthermore, treatment with minocycline also improves the behavioral outcome following JE.

“The most recent outbreak in Uttar Pradesh (concentrated in and around Gorakhpur belt, August-September, 2005) left behind more than one thousand dead, mostly children below 15 years of age” Dr Basu said. Vaccine made by Central Research Institute (CRI), Kasauli is a lyophilized preparation of infected mouse brain tissue. Due to this it is impossible to make it in mass quantity and as expected it is also expensive. Moreover it is only sixty percent efficacious even after multiple boosters.

Dr Basu also noted that multiple boosters not only makes it further expensive but also makes the treatment regime difficult, especially for the follow-up booster doses. It is also noteworthy to mention that at least in India prevalence of JE is predominantly observed in rural/remote and socio economically backward parts of the country. As there are multiple pockets of JE epidemic persists in the country, sometimes it is logistically difficult to transport vaccines in larger quantities from CRI to the location of epidemic. On the other hand minocycline, a tetracycline is easily available in pharmacy or in a primary health care center, in even very rural and remote set up and it is also inexpensive.

“This study has shed more light on the processes that lead to death in children infected with JE virus" Dr Basu said. "We hope that these discoveries will lead to new treatments for JE, which remains a leading cause of death due to encephalitis in entire Asia-Pacific region. Department of Biotechnology is actively considering a clinical trial to use minocycline for JE patients. In addition to Dr Basu, Manoj Kumar Mishra a graduate student of NBRC is also involved in this study. This study is funded by Council of Scientific and Industrial Research, and NBRC is funded by Department of Biotechnology.

Source: Wiley-Blackwell