Binding Of The Dengue Virus To Platelets Biology Essay

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Besides that, human platelets have antibody which is specific for virus so the dengue virus will bind to it and cause the clearance of platelets by immune system. In addition, the virus induces aggregation, lysis and platelet destruction because the spontaneous aggregations of platelets to blood vessel wall cells are pre-infected. Other than that, after the dengue infection, the anti-platelet antibodies formed which will cause destruction of platelet.

If thrombocytopenia happens because of platelet removed from blood in high rate, it will be Disseminated Intravascular Coagulation (DIC). DIC caused by the virus which increases the vascular permeability. The antigen-antibody complexes that circulate in the body will activate the complement and release vasoactive amines, a substance containing amino groups, such as histamine or serotonin, which acts on the blood vessels to alter their permeability or to cause vasodilation. Proteases and lymphokines released and activate complement coagulation cascades and vascular permeability factors during the process of immune elimination of infected cells. (Daniel D Price, MD, 2009)

Rash (Expatriate Malaysia, 2010)

According to Lynsey Keep, 2010, during dengue fever infection, there will be low platelet count which will cause thrombocytopenia. Thus, bleeding occurs under the skin which causes hemorrhagic rash. The rashes will be different according to the stage of infection which is petechial rash, bright red rash and lesions. The appearance of rash will be bright red spots which are known as petechia on the limbs during the early illness. Later stage will cause bright red rash where the skin will appear as bright red. The last stage will be lesions where raised red lesions on the skin.

General weakness (Health Grades Inc, 2010)

Muscular or entire body weakness is general weakness. Fatigue, drowsiness, or fainting can lead to weakness (Health Grades Inc, 2010). This might because low blood pressure. Usually, the brain will not function if the blood pressure too low because blood flow must fight gravity to reach the brain since it is on top of body. Inadequate amount of blood reaching the brain will cause dizziness and faint. If blood pressure is too low, it can damage the brain. Therefore, people will faint to the floor to bring the brain to the level of the heart and blood can flow easily. (George L. Bakris, MD, 2007)

Symptoms of Dengue Hemorrhagic Fever

All the symptoms above and included as following symptoms:

Bleeding (Health Grades Inc, 2010)

If the body platelet counts decrease, serious bleeding can occur inside the body and also outside of the body. Usually, bleeding outside body will be in oral cavity, gums and nose. Internal bleeding will be in stomach, brain, under the skin such as lower legs. There will be blood in stool because of internal bleeding (Expatriate Malaysia, 2010). Small bleeding spots that are purple color will appear if internal bleeding occurs. Since the dengue virus cause bone marrow suppression, the bleeding will be more serious because the platelets not as functional as younger platelets and aged. 200,000-400,000 per cubic millimeter of blood is the normal platelets counts. If the platelet counts below 50,000, patient will have some bleeding symptoms and if the platelet counts below 20,000, patient will have higher risk for bleeding. More serious case will be when the platelets counts are below 10,000. (Dr. Tirgan, 2009)

Acute hepatitis

According to Maria Paula Gomes Mourão, Marcus Vinícius Guimarães de Lacerda, Michele de Souza Bastos, Bernardino Cláudio de Albuquerque & Wilson Duarte Alecrim, 2004 , the main clinical syndrome to show a patient have acute hepatitis is painful hepatomegaly. 30% of the patient have acute hepatitis had gone through hepatomegaly. This symptom mostly appears in DHF patient rather than acute dengue fever patient. To confirm acute hepatitis in a patient, there will be increase in aminotransferase (AST) where 90% of patient had gone through it. According to this journal, the level of aspartate aminotransferase will be higher than alanine aminotransferase. ( as cited in Souza L.J et al.,2002 ; Kalayanarooj S et al., 1997; Mourão M.P.G et al.,2001)

Maria Paula Gomes Mourão et al., 2004 said that the mechanism of this symptom is not fully studied but some believe that the virus, the host and the duration of disease have interaction between each other. ( as cited in Huerre M.R et al.,2001).The virus may have a replication phase in hepatocytes which cause hepatic injury and stimulate apoptosis (as cited in Lum L.C., Lam S.K., George R. & Devi S., 1993; Huerre M.R. et al, 2001; Marianneau P., Flamand M., Deubel V. & Despres P.,1998).

In 2001 during DHF outbreak at Manaus, the capital of Amazonas state in the Brazilian rain forest, there was a case with acute febrile hemorrhagic syndrome and hepatic injury. (Maria Paula Gomes Mourão, 2004)

Hypoalbuminemia

Albumin is a protein synthesized in the liver which functions as a carrier molecule for other molecules that are transported in the blood. Hypoalbuminemia is a condition where the amount of albumin in body is low. This condition happens because of acute hepatitis caused by dengue virus. When, liver disease occurs, the capability of liver to produce albumin will decrease which lead to hypoalbuminemia. (Emma Lloyd, 2010)

Sore throat (Health Grades Inc, 2010)

The symptoms from swollen lymph node could be sore throat. Sore throat mostly happens when mucous membrane that lines the throat is infected or inflamed by virus or bacteria. During this time, more blood flow to the throat to supply more white blood cells and antibodies. This will help to fight the infection and heal the throat. There will be pain during sore throat because swelling of blood vessel in the surrounding tissue will give pressure on the nerve endings in the throat.

Abdominal pain (Health Grades Inc, 2010)

Abdominal pain also leads to low platelet count where excessive bleeding in stomach will cause vomiting of a black, grainy substance that looks like coffee grounds. (Penn State Milton S. Hershey Medical Center, 2010)

Pneumonia (Health Grades Inc, 2010)

Pneumonia is inflammation which occurs in the lungs. Usually the patients who have pneumonia will be having fever, cough, and breathing difficulty. This is because human have immune system that will fight the bacteria or virus that infect lungs. However, there will be some bacteria will reproduce in lungs while immune system try to fight with the infection. The immune response will create inflammation in alveoli where the lungs will be filled with fluid and it become less elastic. This will create another problem because the lung will be less efficient to take oxygen into the blood or remove the carbon dioxide from the blood. Therefore, lungs must work harder to maintain the oxygen level in blood which will lead to breathing difficulty. (WebMD, 2010) There will be cough because the body try cough out the mucus which formed in the lungs. (Dr. sears, 2006)

Low blood pressure and heart rate (Expatriate Malaysia, 2010)

Blood pressure is the force towards the walls of the arteries when the heart pumps blood all over the body. The unit for blood pressure measurement will be millimeters of mercury (mmHg). The reading will be in two numbers where the top number indicates systolic blood pressure and diastolic blood pressure will be the bottom number. The normal blood pressure will be 120/80 mmHg or less than that for both top (120 mmHg) and bottom number (80mmHg).(David C. Dugdale, 2010)

According to George L. Bakris, 2007, Blood pressure can decrease or increase depending on the body condition. Thus, the complementary mechanism in body will control blood pressure when baroreceptors activate the mechanism. Several organs involve in the mechanism which are the heart that function to change the amount of blood pumped, arterioles that will constrict or dilate to change the resistance of blood vessels. Besides that, veins also will constrict and dilate to change their capacity to hold blood, and kidneys are responsible to change the volume of blood in blood vessels by controlling the amount of fluid excreted.

During dengue fever infection, thrombocytopenia cause bleeding where the blood volume and pressure will decrease. At first, the complementary mechanism will control the blood pressure so it will not decrease too much. During low blood pressure, the heart rate will increase, the veins and arterioles will constrict, and the kidney will produce less urine to make sure more fluid returned to the blood vessels. However, if the bleeding is too much or happen too quickly as in Dengue hemorrhagic fever, the compensatory mechanism cannot response quickly. Therefore, the blood pressure will be low and may lead to shock. This is the reason DHF may end in DSS. (George L. Bakris, 2007)

Shock (Expatriate Malaysia, 2010)

Theoretically, multiorgan dysfunction and disseminated intravascular coagulation can cause death to DSS patient. Other than that, metabolic or electrolyte disturbances in a patient with DSS may be accompanied by encephalopathy.

Shock is the critical stage to cause Dengue Shock Syndrome (DSS) which can cause death within 12 to 24 hours. DSS related to DHF because the patient condition will be bad if the fever remain high. Then, the patient will show circulatory failure when the temperature suddenly drop. Thus, for first few days, patients with DHF monitored until their condition is stabilized. (Expatriate Malaysia, 2010)

Vaccination

Currently, there is no vaccination created for dengue fever because researchers found that it is very challenging to create the vaccine. There is little reason such as the vaccine that going to be created must immunize all the four types of viruses. Furthermore, to create the vaccine, laboratory animal model should be used to test the immune response but lacking of it makes the progress difficult. (World Health Organization, 2009) In addition, dengue viruses grow poorly in cell culture so the progress in vaccine development is slow. (Dengue Virus.net, 2011)

Other than that, Antibody Dependent Enhancement is consider another problem. DHF appear in a patient when vaccination provided for only one serotype but another serotype infects the patient. Body immune system will be triggered to the dengue subtype which is infected earlier during dengue fever. The target cell dengue virus attack is macrophage. Thus, when the immune response triggered, the antibodies produced will be specific to that subtype surface proteins that prevents the virus from binding to macrophage cells and enter the cells. (Dengue virus.Net, 2011)

However, our body immune system will be activated when another subtype of dengue virus attack the same individual but the immune system is tricked where the virus is not inactivated by the antibodies that bind to the surface proteins. This is because the four subtypes have very similar surface subtypes. Many macrophages attracted by the immune responses and the virus keep infect them. This situation is referred to as Antibody-Dependent Enhancement (ADE) of a viral infection. As, this situation continues, the viral infection become much more acute. Therefore, our body will keep releases cytokines which end up with DHF because the endothelial tissue become permeable and fluid loss from the blood vessels. (Dengue Virus.net, 2011)

There is little mechanism which cause ADE which is as following. Takada A & Kawaoka Y was written that Fc Receptor (FcR)-dependent is one of the mechanisms for the ADE to occur. According to Ravetch JV , Kinet JP and  Daeron M, the cells that have FcRs on their surface are where the virus and antibody complex will bind. The antibody which have the exposed Fc region will create interaction when bind to FcR on the the cell surface. Macrophages, B cells, neutrophils, monocytes, and granulocytes are the cells of the immune system where FcR will be found. However, there is another mechanism that responsible for ADE in non-FcR behavior cells. This is because not all cells that show ADE are immune cells. Thus, Ross GD said the Complement-mediated ADE is not specific to FcR bearing cells because complement receptors are found on a large variety of cell types. Takada A & Kawaoka Y also written that binding between the Fc region of antibodies and C1q will create Complement-mediated ADE This binding will activate the complement where the complement C3 fragment and viral surface proteins to bind and promote viral attachment. To bring the virus close to the cells, C1q bind to C1qR on the cell surface which will enhance virus attachment. ( as cited in Heather E Eaton, Emily Penny & Craig R Brunetti, 2010)

In the news on wednesday, Malaysian health authorities announced on that the death rate of dengue fever became doubled more than 60 percent this year therefore they were testing for vaccine. In the middle of 2010, there were clinical trials on 300 volunteers and these trials will be continued through December. The Ministry Director General Ismail Merican said, according to Inquirer.net "The vaccine can be used by Malaysian people in the next few year if these studies are successful". (Pat Dulnier, 2010)

According to Lam Sai Kit from the University of Malaya who is the chairman of the forum Dengue v2V, the vaccine can be created by the researchers within 2015 if they receive sufficient funding from governments and private sectors. This forum is to raise fund for vaccine research by recording the dengue cases worldwide. Sanofi Pasteur is pharmaceutical firms is the first firm which wants to produce the first commercial dengue vaccine. Malaysia, Singapore and Thailand are the countries where clinical trials being conducted and will be completed in 2013. However, the vaccine will not be available to public immediately although the trials are successful.(George, 2010)

Diagnosis

There must be some diagnosis to confirm a disease that's how for dengue fever also because the signs and symptoms are similar to typhoid fever or malaria. Thus, blood sample will help to confirm dengue virus. Sometimes the dengue virus detected directly but sometimes there are other blood test such as ELISA (Enzyme - Linked Immunosorbent Assay), HI assay (Hemagglutination Inhibition Assay) and RT-PCR (Reverse Transcriptase- Ploymerase Chain Reaction) are used to identify antibodies, antigens and nucleic acids.

Clarke D H & Casals J, HI test is used most frequently because it is reliable, sensitive, easy to perform and minimal equipment needed. However, Halstead S B it is used for seroepidemiologic studies because HI antibodies persist for long periods which are up to 48 years and probably longer. Detectable levels which is the titer of HI antibody is 10 usually begin to appear by day 5 or 6 of illness. Gubler D J, Sather G E, during secondary infection of dengue infections, there will be immediate anamnestic response and reciprocal antibody titers increase. This increase happens during the first few days of illness, often reaching 5,120 to 10,240 or more. Therefore, the evidence of a current dengue infection in a patient will be titer of ≥1,280 in an acute-phase or early convalescent-phase serum sample. HI antibody will continue to be high for 2 to 3 months in some patients but in most patients, the level will decline by 30 t0 40 days. This methods makes difficult to identify the infecting serotype because specificity is lacking. (As cited Duane J. Gubler, 1998)

According to Chungue E, Marche R, Plichart R, Boutin J P, Roux J, Primary and secondary infections of dengue can be differentiated by using an indirect IgG-ELISA. This test can be used for high volume testing because it is simple and easy to perform. However, there is disadvantage which is lack specificity and shows the same broad cross-reactivity among flaviviruses. Thus, this test cannot be used to identify the infecting dengue virus serotype but its sensitivity slightly higher that HI test. More data accumulated on Ig G-ELISA so it used to replace the HI test.

Acording to Deubel V, Guzman M G, Kouri G, Lanciotti R S, Calisher C H, Gubler D J, Chang G-J, Vorndam A, Vorndam V and Kuno G V, In recent years, Reverse Transcriptase PCR (RT-PCR) has been used for RNA viruses and can develop in laboratory diagnosis. For dengue, this method is very suitable because it provides a rapid serotype-specific diagnosis. The advantages of this method are rapid, sensitive, simple, and reproducible if the procedure controlled properly and can be used to detect viral RNA in human clinical samples, autopsy tissues, or mosquitoes. However, RT-PCR should not be used as replacement for isolation of virus because it is important for characterizing virus strain differences, since this information is significant for viral surveillance and pathogenesis studies. The disadvantage of this method it is highly sensitive to amplicon contamination. Amplicon is a piece of DNA formed as the product of natural or artificial amplification events. False-positive results may occur if the methods proceeded without proper handling.

Knowledge, Attitude and Practices on Dengue Fever

Previously, there are researches of knowledge, attitude, and practice (KAP) survey conducted in two sub-districts of Kamphaeng Phet province, Thailand. In the research, they found that knowledge to prevent dengue fever and the development sites did not change the number unprotected containers in and around their houses. At the same time, they found that more adult Aedes aegypti in the house where the number of unprotected containers is high. Unexpectedly, the houses who used mosquito coils or had screening on doors and windows are the one infected by adult Aedes aegypti. The researchers conclude that there is link between knowledge on dengue prevention and container protection practices but people only take actions towards adult mosquitoes when people experience a mosquito problem.

Other than that, there is a research done in Kampung Datuk Keramat, Kuala Lumpur about knowledge, attitude and practices among the residents. From the research, they found that the resident has poor knowledge, good attitude and moderately poor practices towards dengue fever. The rating poor, moderately poor and good are based on arbitrary cut-off point. The result concluded that good attitude did not correlate with good knowledge and good practices in preventing dengue fever. (Wan rozita WM, Yap BW, Veronica S, Muhammad AK & Lim KH, 2006)

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