parasitic infection and the human host haemostasis

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To illustrate how the parasite can be transferred from an arthropod vector to a human host and how this may lead to a parasitic infection, after evasion.

To explain the haemostatic process used by the host to prevent continuous exposure of blood to the parasite and how the parasite has adapted to hinder this response.

The use of a vector as mode of transport in carrying an infectious agent has evolved into an effective and efficient procedure, exploiting the interaction between the parasite, and that of the host. The widespread use of Arthropods (as a vector), signify it as a model organism for this process. They can consist of hard ticks, mosquitoes and sand flies to name a few, and can provide the vectors for the infectious diseases of, Babesiosis, Malaria and Leishmaniasis respectively. The infectious agent can be part of an adverse cycle, and is continuously transmitted from both the vector and the host. However this requires adequate quantities of the parasitic microorganism present within the host, which can then be ingested into a vector via a blood meal and hence be multiplied, and discharged into a fresh host. This type of transmission is biological as it requires an incubation period. Infectious diseases may also be transmitted mechanically, in which the parasitic agent has contaminated the mouth parts of an arthropod and is then transmitted to a host.

Haematophagous arthropods successfully feed on their hosts, assisted by the various haemostatic, inflammatory and immunodulatory molecules present in their saliva (Andrade et al. 2005). These are known to create a suitable microenvironment for parasitism, disrupting the initial local physiology of the host. Once the tissues and capillaries are lacerated by the parasite, exposing pools of blood in which the parasite gains essential nutrients, the vertebrate host haemostasis is immediately activated. This mechanism prevents further blood loss and involves the triad of vasoconstriction, platelet aggregation and the blood coagulation cascade. However these haemostatic mechanisms are remotely hindered by an anticoagulant, vasodilator, and an anti-platelet which are found within the salivary secretions of blood-feeding arthropods. These pharmacological components can aid the entry of the infectious agents via the puffs of saliva into the human host, which then evade the vascular system infecting the red blood cells. Once infected, the erythrocytes burst, infecting further cells and eventually depleting the oxygen supply.

At the site of lesion in the host, various agonists are released which activates the platelets, due to the vascular damage. Due to the damaged endothelial cells by the piercing of the proboscis threading along the vessel, the collagen becomes exposed, promoting the platelets to adhere to the affected site. This induces the release of cytoplasmic granules which contain serotonin and adenosine diphosphate (ADP). This leads to a positive feedback loop as further platelets are activated and recruited, which enables platelet aggregation and clot formation. The enzyme apyrase also known as ATP-diphosphohydrolase is most commonly known to be released by female mosquitoes, which hydrolyses adenosine diphosphate and adenosine triphosphate (ATP) forming adenosine monophosphate (AMP) and orthophosphate (Steen et al. 2006). This prevents the clotting of blood when taking a blood meal. Along with nociceptor-mediated reflexes and the activation of sympathetic vasoconstrictive neurons, serotonin and thromboxane A2 â€" (also synthesised by the binding of the platelets to the collagen) allow the vessels to narrow. This increases the resistance and slows the rate of blood flow, hence reducing the loss of blood. Many different vasodilatory compounds have been found in the salivary glands of arthropods, the most potent being maxadilan, present in the sand fly Lutzomyia longipalpis.

Blood coagulation is the final event towards the excessive loss of blood and consists of two intricate systems, involving a number of factors. The extrinsic pathway, so called as it is activated via factors from outside the blood, is initiated when blood comes into contact with disrupted tissue. Contrary, the intrinsic pathway, the slower of the two systems, is initiated by intravascular factors, in which high molecular weight kininogen, prekallikrein, Factor XI and XII are exposed to the negatively charged surfaces (Hoffman, 2003). The initiation of the intrinsic pathway, also known as the contact phase, involves the conversion of prekallikrein to kallikrein which in turn activates Factor XII to activated XIIa (Francischetti et al. 2010). This also leads to the synthesis of bradykinin (Ribeiro, 1987). Both systems merge activating Factor X, which can be initiated by either pathway. Once activated, (activated Factor Xa) combines with platelet phospholipids and Factor V which promotes the conversion of Prothrombin to Thrombin. This cleavage also requires a Prothrombin activator, which is activated by platelet thromboplastic factor.

Once thrombin is formed, it allows the polymerization of fibrinogen, a soluble plasma protein, to form long strands of fibrin. The strands of fibrin allow the formation of a mesh-like structure in which the fibrin bridges the platelets and blood constituents together, thus forming a stable thrombus (clot). Furthermore the binding of thrombin to thrombomodulin activates the protein C system (in the presence of protein S), which inactivates Factor Va and Factor VIII. This step acts to ‘shut-off’ the coagulation cascade. Thrombin can be regulated by the presence of the tissue factor pathway inhibitor (TFPI) which binds the tissue factor and Factor VIIa complex. This inhibits the activation of Factor X therefore affects the production of thrombin. In the hard tick Ixodes scapularis, an anti- coagulant known as Ixolaris, has been found to inhibit tissue factor (Moneiro et al. 2005).This protein was identified as a serine protease inhibitor, and when purified and sequenced, it was found to contain Kunitz domains.

Many of the steps above require calcium as a cofactor and phospholipids which become negatively exposed on activated platelets allowing the binding of vitamin-k dependant coagulation factors in the presence of calcium ions. The protozoan parasite Trypansoma Cruzi, infamously known as the cause for Chagas disease, contains a calcium binding protein â€" calreticulin, which binds calcium ions inactivating it, as it does. The presence of calcium is also known to activate the enzyme apyrase, which is found in the salivary secretions of the parasite.

To complete the healing process, serum is extruded from the thrombin, shrinking the clot and it is eventually removed by lysis. This is known as clot dissolution and requires the fibrinolytic system. This system restores the initial circulation of the vessel and is mediated by plasminogen (Nordenhem, 2006).