Here’s some the latest information on Dengue Virus vaccine trials:
The International Health department at Johns Hopkins University is conducting clinical trials in Baltimore, along with international trials later this summer in Brazil, using an experimental dengue vaccine created by NIH.
“The Devil’s Disease, Dengue Fever”, P. McGuire, Johns Hopkins Public Health, Spring 2010 Ed., 2010, pp 16-21.” 1
Why is this important?
“Spiking fever, searing muscle and joint pain, blood seeping through the skin, shock and possibly death—the severest form of dengue fever can inflict unspeakable misery. Once rare, dengue fever now threatens more than 2.5 billion people.” 1
“Dengue is the most rapidly spreading mosquito-borne viral disease in the world. In the last 50 years, incidence has increased 30-fold with increasing geographic expansion to new countries and, in the present decade, from urban to rural settings ….” 2
People’s stories from hundreds and thousands of years ago tell the origins of ka-dinga pepo: the “disease of the devil” (in Swahili) Dengue Virus. Roughly 2000 years ago, one species of mosquito (Aedes aegypti) found new hosts. Those hosts lived in cities and villages along the Nile, recording their experiences for us to read today.
They told tales of a terrible illness that started with a fever and often a rash and easy-bruising. It caused unbelievable pain in the bones and joints, with a special pain emanating from behind the eyes. In its worst forms, the suffering included bleeding from the eyes and oozing blood from the pores. Some recovered, some died. 1
The mosquitoes spread across the tropical and sub-tropical world, eventually stowing away with slave traders and rum-runners, making their way to 17’th century Boston and Philadelphia. By 1780 the famed Dr. Benjamin Rush (a signer of the Declaration of Independence) reported treating an outbreak of “Bone Break Fever” among Philadelphia residents, and the name stuck. 1
Dengue Virus (DV) infections continued to plague much of the Tropical New World until hemisphere-wide mosquito eradication efforts in the 1950’s and 1960’s nearly exterminated it in the Western Hemisphere. 1945 marked the last Dengue epidemic in the United States. Unfortunately, Cuba did not eradicate their Aedes aegypti mosquitoes, while Castro maintained an official public façade that Cuba too should be certified as a Dengue free nation. Cuba’s on-going population of Aedes aegypti mosquitoes and their accompanying Dengue virus appears to have provided an ongoing reservoir of Dengue Virus for re-infecting Caribbean and Central American & South American nations. 2,3
Dengue virus re-appeared in Mexico in 1968 and has spread across almost of Mexico as Aedes aegypti mosquitos moved from Gulf Coastal regions. Since that time, city-loving Aedes aegypti mosquitos and the Dengue Virus have basically been endemic to the Yucatan Peninsula, with confirmed Dengue Virus cases increasing and peaking the past 3 years in Yucatan State. 3
Background Information on Viruses and Why a Dengue Vaccine is Elusive:
Survivors of most viruses are usually immune to subsequent infections, because the survivor makes antibodies that alert the body to resist new future viral invasions. Using this effect, vaccines are usually made from weakened forms of a virus to build similar antibodies for future resistance. Since the eradication of smallpox and near-eradication of polio, vaccine-fostered immunity is a sacred principle of public health.
But Dengue Virus commits sacrilege through a phenomena called antibody-dependent enhancement.
“There’s one thing we are fairly certain of, (i)f you have an antibody to a serotype, say Dengue 1, and you are infected with Dengue 2 virus, your Dengue 1 antibody won’t protect you.” That’s because the antibody binds itself to the new dengue strain, in effect joining forces with the new virus and helping it gain entry into target cells where it can then replicate. 1
At this point the patient’s bloodstream now contains higher levels of the virus than during their first infection. This condition often triggers Dengue Hemorrhagic Fever (DHF) symptoms. Further, any of the four dengue strains (DV-1 – DV-4) can combine with the residual antibodies from any other previously infecting Dengue virus strains to trigger DHF.
It is, according to Scott Halstead, MD, a world authority on dengue research and an adjunct
senior scientist at Johns Hopkins,
“(This is) a most amazing perversion of the immune response. The cells that are supposed to scout out and kill viruses and the antibodies that are supposed to destroy viruses form an unholy complex to defeat our immune system and promote the life of the dengue virus,…” 1
This means that any Dengue vaccine must simultaneously treat all four separate Dengue viruses = a daunting task. A Dengue vaccine would have to cross several hurdles: First, every patient must develop a good antibody response to each of the 4 Dengue serotypes. Second, every patient must maintain sufficient levels of antibodies to each of the 4 Dengue serotypes, even though the levels of antibodies to each Dengue strain typically decline at different rates.
The era of Walter Reed and his heroic cohorts has passed, and it is no longer acceptable to prove new vaccine, by exposing previously vaccinated volunteers to even one strain of live Dengue Virus, the challenges of testing long-term vaccine efficacy against 4 serotypes presents special challenges.
Hope beckons from another avenue though for Dengue Virus: Malaria appears much more sophisiticated with 6,000 genes, and is able to replicate its DNA on its own. In contrast Dengue has only 10 genes and must use the genetic replication machinery of the Aedes Aegypti to replicate. This means that the Dengue virus makes its host mosquitoes sick, and it may be possible to genetically modify Aedes aegypti mosquitoes’ immune systems to resist Dengue attacks, breaking the cycle of Dengue transmission.
But that raises other issues, no?
1 “The Devil’s Disease, Dengue Fever”, P. McGuire, Johns Hopkins Public Health, Spring 2010 Ed., 2010, pp 16-21.
2Dengue: guidelines for diagnosis, treatment, prevention and control — New edition, WHO and the Special Programme for Research and Training in Tropical Diseases (TDR), 3′rd Edition report, ISBN 978 92 4 154787 1, 2009.
3A Timeline for Dengue in the Americas to December 31, 2000 and Noted First Pccurrences”. J Schneider, MPH and D Droll, Pan American Health Organization: Division of Disease Prevention and Control, June, 2001, 99 1-20.