dengue vaccine, developed after extensive research, now faces hurdles, with
reports emerging of possible severe dengue infection occurring in some
vaccinated individuals who were previously not exposed to dengue
- Emerging data
suggests that the dengue vaccine increases the risk of severe disease and
hospitalization due to dengue infection in individuals who were not
previously exposed to the virus.
- The infection is
not caused by the vaccine per se,
but by reinfection by a dengue virus from the environment.
- The issue could
be resolved by testing individuals for prior infection before the
administration of the vaccine.
. The issue
has been highlighted in an editorial published in The Lancet Infectious Diseases.
dengue vaccine, CYD-TDV
(brand name Dengvaxia) was recently approved in 19 countries to protect
individuals from dengue infection in the age group of 9 to 45 years
, with the
hope that it would bring the infection under control in places with high burden
of the disease. The vaccine is administered in three doses with a gap of 6
months between doses.
‘An increased risk of severe infection that could occur in some individuals who take the dengue vaccine has prompted the World Health Organization to provide recommendations on who is safe to get the vaccine.’
data provided by the manufacturer suggests that the vaccine can cause severe
dengue in some individuals
. The finding has prompted the Philippines, one
of the countries that had approved a regional mass vaccination program, to
withdraw the program.
reason for this unexpected adverse effect can be explained based on the way the
body reacts to a natural dengue
. Dengue infection is
caused by four subtypes or serotypes of the virus. An infection with one
serotype provides life-long immunity against the specific type of dengue virus,
but a second infection by a different serotype can occur and often results in a
serious disease. A third or fourth infection, however, is usually mild.
It is therefore
suggested that a similar reaction occurs with vaccination as well. If the individual was never exposed to the
virus earlier, the vaccine acts as the first or primary infection
subsequent natural infection thus becomes a second infection and is more likely
to be severe. However, if the individual
was previously exposed to the virus, the vaccine acts as a second infection,
which cannot be severe since the virus is inactivated in the vaccine
a future natural infection acts as the third or fourth infection, which is
One of the reasons why
the dengue vaccine was not approved for use in children younger than 9 years
was that clinical trials revealed an
increased chance of hospital admission for dengue in children between 2 and 5
years in the third year following the administration of the vaccine
. It is
possible that the younger children were not exposed to the virus earlier. The
vaccine therefore acted as a primary infection and a subsequent natural second
infection was more likely to be severe.
In view of the above,
blood tests were carried out by the manufacturer on samples obtained from
vaccinated individuals to find whether the individuals were exposed to dengue
infection before the vaccination. They concluded that:
- The vaccine
protected people who were exposed to the dengue virus before the vaccination,
against severe dengue infection and hospitalization for 5 years
- People who
were not exposed to the dengue virus before the vaccination were more
likely to suffer from serious dengue infection following the vaccination. The risk
was highest in the third year following the first dose of the vaccine
Information on the risk
of severe infection after a period of 5 years is currently not known. It is,
however, clear that the dengue that occurs following vaccination is not due to
the virus in the vaccine per se,
but due to a subsequent natural infection.
the vaccine appears to protect more number of individuals from severe dengue
infection than harm them in regions with high burden of the disease
considering the fact that even a small number of individuals can suffer from
serious dengue following the vaccination raises the question whether the
vaccine use should be continued.
World Health Organization (WHO) has recommended that vaccine should be
administered only to individuals who were earlier infected with dengue.
individuals, however, may have had an asymptomatic disease or a mild disease
that could have be mistaken for any other viral infection, and may not even
know that they had a previous infection.
problem can be partially addressed by first testing individuals for a previous
infection, and then administering the vaccine only if they test positive
. A rapid
diagnostic test that can quickly and accurately measure the infection status at
a primary care level before the administration of a vaccine, however, is
currently not available. Thus, the
development of a test to screen individuals who should receive the vaccine is
the need of the hour
the WHO advises the use of the vaccine only in those who have a proven
infection, either by a diagnostic test or a previous documented medical history
of an infection.
The WHO is expected to review and re-state its stand on the
use of dengue vaccine in April 2018. The publication will hopefully provide
more clarity on the issue.
Dengue is a viral
infection spread through the bite of the Aedes mosquito. The virus exists as 4
different serotypes. While majority of the cases result in mild illness and
respond to symptomatic treatment, sudden death due to complications like
bleeding and shock are not uncommon. Currently, no definite treatment for
dengue exists. Platelet transfusion and fluid infusion has been life-saving in
several cases. There is some emerging evidence about the protective effects of
papaya leaf extract to improve platelet counts in dengue patients. Prevention
from dengue is mainly directed at preventing mosquito bites.
- The dengue vaccine dilemma. The Lancet Infectious Diseases 2018: 18(2):123. DOI: http://dx.doi.org/10.1016/S1473-3099(18)30023-9
- Updated Questions and Answers related to the dengue vaccine Dengvaxia® and its use - (http://www.who.int/immunization/diseases/dengue/q_and_a_dengue_vaccine