The Symptoms Of Tick Borne Encephalitis

Essay add: 22-10-2015, 20:34   /   Views: 173

Tick-borne encephalitis virus (TBEV) is mainly transmitted by a tick bite whose saliva contains virus, by ingestion of milk products containing TBEV, or by inhalation of TBEV. The saliva itself is composed of various substances that prevent blood coagulation, relax and widen blood vessels, and prevent inflammation and cause immunosuppressive effects, which allows the tick to continue feeding for 2 to 20 days. The virus enters the host almost immediately, but the concentration of virus in tick saliva has a 100-fold increase with long term feeding. TBEV has been grouped into three subtypes using serological techniques: a European subtype, a Siberian subtype, and a Far Eastern subtype (1).

The Ixodes ricinus tick transmits the European subtype and Ixodes persulcatus transmits the Siberian and Far Eastern subtype (1).The symptoms of Tick-borne encephalitis (TBE) depend on which TBEV subtype has caused the infection (1). Each subtype has approximately the same time period of 7 to 14 days between time of infection and appearance of symptoms. Typical symptoms range from fever, nausea and vomiting, muscular pain, fasciculations and numbness in some limbs, and some neck stiffness (2). Also ataxia is very common among TBE patients followed by complete loss of muscle function of some limbs (3).

Following the incubation period (7-14 days) for the European subtype virus, symptoms of fever, fatigue, headache and body ache appear during phase one and then disappear for one week. New symptoms of meningitis and meningoencephalits appear during phase two and can progress into postencephalitic syndrome (1). Far Eastern subtype virus impacts the CNS the most and causes focal meningoencephalitis or polyencephalitis, fatigue, loss of consciousness, and may permanently damage neurons throughout the CNS. The Siberian subtype virus has a mild acute period, but typically causes chronic Tick-borne encephalitis (TBE). The European subtype is biphasic and has a low fatality rate of 1-2%, but the Far Eastern subtype has a fatality rate of 20-60% and the Siberian subtype is 6-8%.

Far Eastern subtype has a higher fatality rate due to its small cell tropism for neurons of the CNS, and neuronal degradation occurs in result to viral replication in these cells, whereas European subtype targets the lymphoid tissues and appears in the brain 6 to 9 days after infection. Siberian subtypes are able to slowly reproduce and appear asymptomatic, and chronic TBE studies with Syrian hamsters show that TBEV can be isolated up to 383 days post-infection (2). TBE mainly causes severe neurological symptoms due to its high affinity for infecting cells of the central nervous system.Once the Tick-borne encephalitis virus has entered the host, viral replication begins in dendritic cells (DCs) in the skin.

The virus enters the lymphatic system and is transported to nearby lymph nodes where replication in lymphatic organs continues and results in viremia. TBEV in the blood further spreads the virus to extraneural tissues and leads to breaching of the blood-brain barrier. Intensity of neuroinvasiveness can be rated, for example, a virus with low neuroinvasiveness will have not cause viremia in peripheral tissues.

Apparent neuronal changes were observed in mice infected with TBEV such as: necrosis and apoptosis of neurons, inflammation, enlarged lysosomes, and branching/grouping of endoplasmic reticulum membranes (3).Studies on mice infected with TBEV have shown that encephalitis may be caused by the intense host immune response. Following the tick bite with infected saliva, TBEV infects dendritic cells in the skin, which activate the adaptive immune response by displaying antigen-presenting cells (APCs) on MHC II proteins on the cell surface. Dendritic cells in the blood also present APCs to help initiate an immune response, but are also responsible for shuttling TBEV to the lymph nodes (1).Once infected, nearly all mammalian cells are capable of recognizing pathogen associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs).

Type I interferons (IFNs) quickly detect pathogens via PRRs and activate the innate immune response. Also, Type I IFNs trigger an antiviral state and initiate the synthesis of at least 300 cellular proteins. Tick-borne encephalitis virus falls into the Flavivirus group, who are vulnerable to type I IFNs rapid immune response, so TBEV has evolved its NS5 protein to block the signal of type I IFNs after infection. Macrophages will also display antigens by upregulation of MHC II to activate CD4+ T-cells and therefore activate B cells to produce antibodies in CSF. TBEV has been shown to induce macrophages to produce Nitric Oxide (NO), but the use of NO by TBEV is not well understood.

Researchers do know that macrophages are highly susceptible to infection by TBEV and are necessary for localized replication of virus before complete viremia is accomplished. Therefore, macrophages may largely contribute to the rapid spread of TBEV throughout the bloodstream. Neutrophils also participate in phagocytosis and contribute to the spread of TBEV to peripheral tissues, but have not been shown to support viral replication. Natural killer cells are capable of clearing infected host cells, but TBEV has evolved itself to block NK cells.

TBEV replication in lymph organs leads to viremia and spread of virus to peripheral tissues and crossing of blood-brain barrier, but if the host issues a successful humoral immune response with TBEV-specific IgG and IgM antibodies, viremia and spread of virus can be stopped and the infection can be cleared by the immune system (1).

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