by kladmin | January 15th, 2008
Chris English
Dengue Fever, named after a Spanish version of the Swahili phrase ki denga popo or “sudden possession of a person by a spirit,” was first identified in the 1940s when it became a concern to the armies fighting in the Pacific and Asia; the disease was causing large numbers of non-combat casualties. Japanese scientists first identified the virus in 1943, quickly followed by U.S. researchers a year later. By 1956 its four serotypes had been identified and every outbreak of the disease since has been due to a virus belonging to one of these original four.
There are 50 – 125 million cases of infection in more than 100 Latin American countries, the Caribbean, Eastern Mediterranean, South-east Asia, Western Pacific and Africa each year. Recently, several Latin American and Caribbean countries have experienced Dengue outbreaks with serious consequences. This is an appallingly high rate of infection, considering there are only 2.5 billion people living in Dengue-epidemic areas. Dengue Fever is transmitted by two species of female mosquitoes — Aedes aegypti and Aedes albopictus — and causes “break-bone” fever with the risk of hemorrhagic fever, Dengue Shock Syndrome and death.
The most worrisome aspect of its resurgence is that it has spawned an increase in the frequency and severity of Dengue Hemorrhagic Syndrome, a severe complication of the disease normally only arising upon re-infection. Typically, when diseases first crossover to other species they are at their most severe (syphilis is a good example of this), and over the years they become less severe as they adapt to a new host. Dengue Fever appears to be running against the tide, making it a greater threat to public health.
The current major preventive strategy against Dengue Fever, mosquito control, entails spraying larvae and adult mosquitoes with insecticides and reducing mosquito breeding areas. Despite some limited success in a few countries, e.g. Singapore, widespread mosquito control efforts are difficult to sustain, as evidenced by the continued spread of the disease. The development of a vaccine offers the potential for effective prevention and long-term control. However, to date there are no approved Dengue vaccines. There are several vaccine candidates in trials, but as they are produced by attenuation of original or wild type viruses they all have significant limitations: attenuated and inactivated viruses have stability problems and are generally unsatisfactory.
A new start-up company, ARBOVAX Inc., is focusing on developing a novel technique that exploits differences in cell membranes of insect and mammalian cells. Viruses carried by insects must be able to interact with these different membranes in order to produce virus particles in the two different hosts.
The technology involves producing a modified virus that will reproduce normally in insect cell lines but will not do so in mammalian cells. By making several deletions in the part of the virus involved in penetrating the cell membrane, a stable clone or replica may be produced that has all of the functional properties of the wild type only when it is grown in the insect cell. When a mammal is exposed to the insect-grown virus it will induce a strong immune reaction in the patient but will not cause disease.
Since the virus does not replicate in patients’ cells it is safer to use. It is also more effective because it is immunologically indistinguishable from the wild type and the cost to produce is expected to be significantly less as the modified virus can be easily grown in a standard insect-cell reactor.
The emergence of the travel vaccine market and an increasing awareness of the economic impact of many diseases such as AIDS, Malaria, and Dengue Fever has resulted in the recognition that certain neglected diseases, including Dengue, West Nile Virus, Japanese Encephalitis and Yellow Fever, which once represented economically unviable markets are now financially sustainable. It is hoped that these new frontiers in vaccine development may open the door to the eradication of this virus once and for all.
Chris English lives in St. Kitts and is currently Chairman of the Board, ARBOVAX, Inc. More information on this technology may be obtained at http://www.arbovax.com.
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