The planet of Earth is rich with eternal beauty but the prosperity and tranquility provided by the nature to this part of the universe is in a shambles today. High population growth rate, urbanization, global warming and new environmental constraints are evolving the issue of disease outbreaks and dengue fever is one of them. South Asia, South East Asia, Africa and South America are those hapless parts of the globe in which the maledictions of dengue virus are yet to be eradicated. This is a matter of great concern which must be solved by the brains and brawn of international community.

The dengue virus has exposed itself in 5 serotypes throughout the globe inter alia DENV-1, DENV-2, DENV-3, DENV-4 and the fifth type DENV-5, which was announced in 2013. The virus is particularly transmitted by mosquitoes called aedes aegypti and aedes albopictus. Humans are the primary host of the virus. A female mosquito that takes a blood meal from a person infected with Dengue fever becomes itself contaminated with the virus which also includes her salivary glands. When a mosquito carrying dengue virus bites a person, the virus enters the skin together with the mosquito’s saliva. The virus binds to the Langerhans cells inside the skin. DC-SIGN, a non-specific receptor for foreign material on Langerhans cells seems to be the main point of ingression for Dengue Virus. The virus replicates inside the cell and the newly formed viruses bud on the surface of the infected cell which are released by exocytosis. The unleashed viruses then bind to and irrupt into white blood cells (WBCs) such as monocytes and macrophages. The white blood cells respond by producing a number of signalling proteins such as cytokines and interferons. The virus further infects stromal cells of bone marrow which lead to bone marrow dysfunction and subsequently reduced number of platelets. Fever, myalgia, headache, nausea, vomiting, diarrhoea and a rash are the initial symptoms of dengue fever which are followed by petechia, positive tourniquet test and mild bleeding from the mucous membranes of the mouth and nose. In some cases, the infection may progress to the dengue shock syndrome and dengue hemorrhagic fever. Laboratory tests for timely detection of infection include virus isolation in cell cultures, nucleic acid detection by PCR, NS1 antigen detection and specific antibodies detection (IgM) and low platelets count.

Currently there is no licensed vaccine and antiviral drug to beat the perils in the affected regions. Various research institutes and pharmaceutical companies should be sponsored and patronised for swift invention of an effective vaccine and antiviral drug. Research is to be initiated to develop a therapeutic tool that can interfere with the interaction of Viral E protein with several molecules like ICAM3-grabbing non-integrin, CD209, Rab5, GRP78 and the Mannose receptor of the target cell. The preparation and production of synthetic pentavalent Human Dengue immune globulins (HDIG) shall be a quantum leap in therapeutic arena. Studies should also be conducted to ferret out any role of Sofosbuvir (SOVALDI) & Ledipasvir in the management of Dengue Fever. The arena of discovery of small molecules that can target viral enzymes which are essential for virus replication in infected cells needs further exploration. Presently, the most important fields of interest are the practical invention and discovery of Protease inhibitors, RNA dependent RNA polymerase inhibitors, 5- Capping process inhibitors and drugs that can target the relation between NS1 and Toll Like Receptor 4 (TLR4). In some studies, interfering with viral replication using Peptide-Conjugated Phosphorodiamidate Morpholino Oligomers (P-PMOs) have also been proposed and are effective in cell culture.

Elimination of the dengue virus demands both long-term and short-term plans. The affected countries shall undertake an exercise of screening their citizens for timely detection of the virus and isolation of the affected individuals. A paradigm of placement of the guppy (poecilia reticulata) or cope pods in standing water should be made a prodigious affair throughout the globe. Genetically engineered mosquitoes for eradication of dengue virus can also be helpful in minimization of purgatory scenes.

Lastly, studies should also be conducted to observe any therapeutic role of modified dengue virus in the management of essential thrombocythemia and polycythemia vera. In short, it is concluded that the preservation of world as a safe haven for humanity demands the initiation of great leap forward plans to make the future free from gory incidents.

—The writer Dr Faisal Ali serves as medical officer at Employees Social Security Institution, Abbottabad.