**12. Potential treatments in the future – anti-virals**

viral agent, 3% a confirmed bacterial agent, 1% a confirmed parasitic agent, 10% a non-infec‐ tious etiology and 12% a possible etiology identified. 3% had a non-encephalitis infection identified. Nevertheless, CEP is not population based and the study group consisted of diag‐ nostically challenging cases. Therefore, the rate of unknown etiology cases may be an over‐

Diagnostic strategies that have emerged recently include MassTagPCR, panmicrobial DNA microarrays and high-throughput DNA pyrosequencing [82]. MassTag PCR is a multiplex PCR assay utilizing primer pairs targeting highly conserved gene sequences that represent a wide variety of potential pathogens. The primer pairs have been tagged with MassCodes that are used to identify the etiological agent. There are different MassTag PCR systems with different primers for different clinical specimens and presentations. Clinical use of this method has demonstrated effectiveness in identification of pathogens [90-93]. Panmicrobial DNA microarrays utilize a single chip with numerous highly conserved gene sequences, permitting the swift identification of pathogens similar to that of MassTag PCR [94, 95]. Clinical use of this diagnostic method has also demonstrated efficacy in pathogen identifica‐

High-throughput DNA pyrosequencing on the other hand, does not make use of highly con‐ served gene sequences. Instead, it uses random primers to amplify all RNA after removing human chromosomal DNA from the sample [99]. Amplification products are then se‐ quenced via pyrosequencing wherein DNA polymerases synthesize complementary strands to the amplified products and each enzymatic attachment of a complementary nucleotide re‐ sults in an emission of a light signal. The light signal is recorded and the sequences are iden‐ tified and subsequently analyzed to look for pathogens. This technique allows for

At present, only herpes simplex encephalitis, one of the more prevalent infective encephali‐ tis, has a specific treatment validated by scientific research. It is treated with aciclovir [101].

Currently, intravenous immunoglobulin (IVIG) is administered to patients with severe HFMD [5]. Enteroviruses are cleared from the host by antibody-mediated mechanisms (22), and IVIG is an effective treatment option. Various routes of administration have been docu‐ mented including intravenous, intrathecal and intraventricular with different degrees of

However, the best defence would be prevention through vaccination, especially in the case of rabies, polio, mumps and measles. Vaccination may be an option to prevent infection by

Effective treatment is lacking for other viruses and mainly symptomatic in nature.

**11. Potential treatments in the future – vaccines**

estimate when extrapolated to the general population.

tion [96-98].

272 Encephalitis

**10. Treatment**

success [102-104].

identification of novel pathogens [100].

Ribavirin, a broad-spectrum antiviral synthesized by ICN pharmaceuticals, Inc., USA inhib‐ its the replication of a variety of enteroviruses. Studies on EV71-infected mice has shown that ribavirin can reduce mortality by reducing the viral loads in tissues. The required dos‐ age of ribavirin is close to the initial dose of the drug administered intravenously to treat patients with encephalitis caused by Nipah virus [106]. Given these results, ribavirin may be, in combination with interferon, deployed to combat potentially fatal EV71 infection. In‐ terferon has a synergist effect and this combination is already adopted as a standard therapy for HCV-infected patients [107].

Pyridyl imidazolidinone is a novel class of EV71 inhibitor [108]. It was first identified using computer-assisted drug design. It targets EV71 capsid protein VP1 and time course experi‐ ments on one of the pyridyl imidazolidinones, BPR0Z-194, have shown that viral replication is effectively inhibited in early stages, suggesting that the compound inhibits adsorption of virions and/or viral RNA uncoating [108]. Resistant strains do exist, and sequence analysis has demonstrated that a single amino acid alteration at position 192 of VP1 confers resist‐ ance to BPR0Z-194 [108].

Pleconaril, an anti-viral produced by Sterling-Winthrop, Inc., USA incorporates itself into the capsid of enteroviruses and blocks the virus from docking to cellular receptors and uncoating to release RNA into the cell. It targets VP1 and has already passed the last stage of clinical trials [109]. Results are promising with pleconaril showing antiviral ef‐ fects for most enteroviruses [109, 110]. Presently, there is an ongoing study on the effica‐ cy of pleconaril in enteroviral sepsis syndrome in neonates [111]. The National Health Research Institutes (NHRI) in Taiwan has reported a number of virtual compounds with similar stable conformations and preliminary studies have identified a few promising imidazolidinone derivatives.
