Dengue fever is caused by four
closely related serotypes DV1, DV2, DV3, D4 viruses of genus flavivirus carried
by mosquito Aedes aegypti most abundant in tropical and sub-tropical regions.
Dengue infection can result in a range of clinical manifestation from
asymptomatic infection (80%) to dengue fever (10-15%) and the severe disease (5%
-10%) of dengue hemorrhagic fever or dengue shock syndrome, which are fatal if
not managed properly. Infection to one serotype produces life-long immunity, by
the production of antibodies, against infection by the same serotype but only
short term and partial protection against infection with other serotypes.
The presence of antibodies of one serotype pave the way for dengue hemorrhagic
fever through immune enhancement as virus/non-neutralizing antibody complexes
preferentially engulfed cells of immune system ,enabling the virus
multiplication unchecked and thus the teeming population of virus results in
severe infection often lethal. So, development of vaccine which produces “immune
response” against all four serotypes is absolutely necessary as about 3 billion
people of more than 110 countries (every second person) are at risk, 230 million
gets dengue infection annually, 2 million (less than 1% of dengue patients)-
mostly children – develops severe form of dengue hemorrhagic fever. About 2
million gets hospitalization and 25000 dies. Mortality is about 5% without
treatment and 1% with adequate treatment.
Dengue has increased 30 fold in last 50 years. Most countries are relaying on
aged long mosquito control methods. They are not learning lesson from history;
mosquito is more than 150000000 years old specie and had sustained in the
extreme severity of conditions of all ages that mankind even not dare to think.
Then how it will succumb to these mild measures of mankind, so an inside remedy
is to be provoked to combat the onslaught of this tiny fierce creature at
molecular level, anti dengue vaccine and anti viral drug is the viable solution.
Vaccination saves about 2.5 million people every year but more than 2 million
people still die due to lack of access to vaccine.
Look at Sri Lanka where mortality rate had diminished to half this year due high
level training, awareness campaign, introduction of new testing devices and
strict observance of precautionary measures. On the other hand, dengue cases
have increased than previous years with 11, 250 until April along with 55
deaths. In spite of cleaning operation, garbage disposal, persistent fogging,
spraying Bti (bacillus thuringiensis israelenis-are bacteria which infects and
kills mosquito larva) and strict surveillance of mosquito colonized areas and
stern execution of dengue control laws as 2191 dengue linked arrests and about
four million rupees fine were collected until April from mosquito breeders. The
shrewd mosquitoes have found new places to breed in cemented walls instead of
usual breading places of home garden, water channels, etc. So, development of
vaccine is indispensable to check the spread of disease, said Dr. Paba
Pallihawardene, head of entomological department.
She disclosed, “We will have anti dengue vaccine by 2015, trials are underway,
as all other methods of controlling the spread of dengue have proved not
effective.”
The preparation of vaccine to counter all serotypes has one major threat that
vaccine will enhance the risk of severe disease through antibody-dependent
enhancement (ADE). So an ideal vaccine should be safe, efficacious, wraps all
variants of viruses, doesn’t contribute to ADE, transportable, easily storable
and inexpensive.
Apart from Sri Lanka, Chinese are focusing to produce tetravalent vaccine by
integrating four monovalent components and developed a genetic vaccine based on
novel adeno-associated viral (AAV) vector expressing the carboxyl-terminal,
truncated envelope protein of dengue virus. AAV was injected into mice and
antigen of dengue virus was produced that induced production of antibody and
thus long lasing immunity developed against dengue virus.
Philippine is also struggling to produce anti dengue vaccine in the laboratories
of the Department of Health (DOH) in Cebu and Laguna by joint efforts of
Filipino and foreign experts. Dr Janario, Director DOH said: “Philippine was
chosen because it is the one of the nation affected by dengue. We have experts,
the facility, the data and the surveillance system. There are four strains of
dengue and you can find them all here.”
In Cuba, vaccine is currently being tested on monkey and will advance to
clinical trial on human if the results are satisfactory, said Dr. Gerardo
Guillen, Research Director of International Centre for Genetic Engineering and
Biotechnology (Cigb). Dr. Guillen disclosed vaccine has effectively controlled
the multiplication of virus in monkeys. Vaccine is designed to act on all the
four variants of the dengue virus. Cigb is working with France’s Pasteur
institute to develop the vaccine.
At present, many international pharmaceutical companies are developing vaccines
by using the virus itself. It is an old method to use infectious but attenuated
virus to produce strong long lasting immunity.
Sanofi Pasteur of Lyon, France has developed a live attenuated virus vaccine
that produces antibodies against all four serotypes in preliminary studies, but
for some reason, one strain of virus (DEN-2) was still able to infect children
who received the vaccine. Now a much larger trial involving 31,000 adults and
children of 10 different countries of Asia and Latin America is under way. Full
details of study are expected in scientific paper this month.
Sanofi is five years ahead of other vaccine producing ventures. Reuter revealed
that 4000 Thai children have received vaccine and if their body developed
sufficient immunity countering all four strains, Sanofi will submit his therapy
for medical vetting in the USA in November 2012. Sanofi has invested $ 440
million to build a pharmaceutical factory in France, one of the largest
pharmaceutical companies of the world, to manufacture vaccine. Health experts
are optimistic that the vaccine could now go to market in 2014 or even earlier.
Health experts fear that heavy commercial investment could mean that Sanofi’s
vaccine will be costly, which is a letdown as dengue normally afflicts those who
cannot afford. Health experts also believe that company will achieve both
medical and commercial successes as 3 billion at risk people are waiting for
vaccine.
Sanofi product will be delivered in three separate shorts, in a span of 12
months in order to effectively fight the dengue virus. Health experts lamented
this long period for patient to combat the disease and more window of
opportunity for the virus to sow terror. However Duane Gubler USA expert awith
40 years experience of tracking dengue movement said, “Everything they have done
so far looks very good.” His compliment made Sanofi cheerful with hope of
getting one billion euro annually once the dengue cure has been rolled out
successfully. Sanofi disclosed that vaccine has yet to be given commercial name.
The journey of developing vaccine has been started in 1940’s but now we are
seeing the blurred view of our coveted destination. One can infer and hope from
the above developments that anti dengue vaccine will be available in market
soon. In a nutshell, we can say: “Drug to detonate; deadly, dangerous, dreadful,
damnable dengue is developing…. and will be divulged then dispersed for
distribution, for the disappointed, disheveled diseased”.