Dengue fever is a tropical disease caused by the dengue virus transmitted by mosquitoes. Symptoms of dengue infection include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases the disease develops into the life-threatening dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously low blood pressure occurs.
The dengue virus is a single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus. Four serotypes are identified, all of which can cause the full spectrum of disease.
Severe reduction of blood platelet counts and resultant hemorrhages and shocks are the greatest threats posed by dengue viral fever.
The reason that some people suffer from more severe forms of dengue, such as dengue hemorrhagic fever, is multifactorial. Different strains of dengue viruses interacting with people with different immune backgrounds lead to a complex interaction. Among the possible causes are cross-serotypic immune response, through a mechanism known as ‘antibody-dependent enhancement’, which happens when a person who has been previously infected with dengue gets infected for the second, third or fourth time. The previous antibodies to the old strain of dengue virus now interfere with the immune response to the current strain, leading paradoxically to more virus entry and uptake.
Developing a vaccine against the disease is challenging. With five different serotypes of the dengue virus that can cause the disease, the vaccine must immunize against all five types to be effective. Vaccination against only one serotype could possibly lead to severe dengue hemorrhagic shock when infected with another serotype due to antibody-dependent enhancement. When infected with Dengue virus, the immune system produces cross-reactive antibodies that provide immunity to that particular serotype. However, these antibodies are incapable of neutralizing any other serotypes upon reinfection and actually serve to increases viral infection. When macrophages consume the ‘neutralized’ virus, the virus is able replicate within the macrophage. In all, these cross-reactive, ineffective antibodies ease the access of these viruses into macrophages, which induces the dengue hemorrhagic fever. A common problem faced in dengue-endemic regions is when mothers become infected with dengue; after giving birth, offspring carry the immunity from their mother and are susceptible to hemorrhagic fever if infected with any of the other four serotypes.
Platelets are produced in the megakaryocytes, the bone marrow cells that bud off large numbers of platelets.
Thrombopoietin is a glycoprotein hormone produced by the liver and kidney which regulates the production of platelets. It stimulates the production and differentiation of megakaryocytes leading to production of platelets. This cellular development process that leads to platelet production is known as ‘megakaryocytopoiesis’.
Thrombopoietin is produced in the liver by both parenchymal cells and sinusoidal endothelial cells, in the kidney by proximal convoluted tubule cells. Small amounts are also made by striated muscle and bone marrow stromal cells.In the liver, its production is augmented by interleukin 6 (IL-6). However, the liver and the bone marrow stromal cells are the primary sites of thrombopoietin production.
Thrombopoietin regulates the differentiation of megakaryocytes and platelets. For initiating this process, thrombopoietin molecules have to bind to the specific binding sites of receptors located up on the megakaryocute cell membranes.
Reduction in platelet counts happen either due to the deficient production of thrombopoietin hormone in the liver, or due to the inhibition of receptors on the megakaryocytes so that thrombopoietin molecules fail to bind to the receptors and initiate the biochemical processes involved in ‘megakaryocytopoiesis’.
During DENGUE FEVER, viral envelope glycoproteins competitively bind to the thrombopoietin receptors of megakaryocyte cell membranes and inhibit them, thereby preventing thrombopoietin molecules from interacting with the receptors. This leads to disruption of platelet production or ‘megakaryocytopoiesis’.
Molecular Imprints or potentized ‘dengue viral glycoproteins’ can act as artificial binding sites for the viral glycoprotein molecules and remove this molecular inhibition, and reactivate the biochemical processes required for platelet production.
Molecular imprints of ‘thrombopoietin’ molecules also can act as artificial binding sites for the viral glycoproteins and remove this molecular inhibition, and reactivate the biochemical processes required for platelet production.
Molecular imprints of any drug substance that have functional groups SIMILAR to the ‘dengue glycoproteins’ can also act as artificial binding sites for the viral glycoproteins and remove this molecular inhibition, and reactivate the biochemical processes required for platelet production. This SIMILARITY can by identified by SIMILARITY OF SYMPTOMS they produce during drug proving in healthy individuals using MOLECULAR forms of those drug substances.