Dengue

Paul R. Earl

Facultad de Ciencias Biológicas

Universidad Autónoma de Nuevo León
San Nicolás de los Garza, Nl, Mexico
 Generalities.
DENGUE (DEN) is a positive-
stranded RNA virus that is spread by
the bite of an infected female mosquito
which carries dengue virus after
feeding on the blood of an infected
person. Dengue is a mosquito-borne
disease, and the objective is to stop the
transmission of the pathogen.
The infected mosquito is commonly Aedes
(Stegomyla) aegypti, and depending on the
geographic area A. albopictus and A.
polynesiensis are also seriously involved.
Replication of positive strand flaviviruses
is mediated by the viral RNA-dependent
RNA polymerases (RdRP). The mosquito
vectors and 4 DEN viruses are found
throughout the subtropics and tropics
where over 2.3 billion human hosts are at
risk, especially children.
Dengue can be prevented by

1) elimination of mosquito
breeding places,
2) prevention of mosquito bites
and
3) vaccination of all persons
against all 4 serotypes, DEN 1-4.
Annually, over 100 million cases of
primary dengue fever and over
450,000 cases of dengue
hemorrhagic fever (DHF) and shock
syndrome (DSS) occur DHF/DSS
many fatal) is the leading cause of
hospitalization of children in Asia.
A sick person needs to be
diagnosed and treated early,
and a rise in vector population
must be controled early. Much
of the essential knowledge on
dengue fever has now been
presented. Health education is
the crucial aspect.
 Symptoms.
As soon as the public understands the
mosquito transmission of dengue, they
should learn the symptoms. Dengue fever
has 1) sudden high fever, 2) severe frontal
headache, 3) pain behind the eyes that
worsens with eye movements, 4) muscle
and joint pains, 5) loss of sense of taste and
appetite, 6) measles-like rash over the
chest and upper arms, and 7) nausea and
vomiting. Breakbone fever is one name for
dengue.
DHF/DSS has 1) severe and
continuous stomach pains, 2) pale,
cold or clammy skin, 3) Bleeding
from the nose, mouth and gums ±
skin bruising, 4) vomiting often ±
blood, 5) sleepiness and restlessness,
6) constant crying, 7) excessive thirst,
8) rapid weak pulse, 9) difficulty in
breathing, and 10) fainting.
DHF is the most fever form of
dengue with hemorrhage and the
tendency to develop shock. DHF
presents a high continuous fever
of 2-7 days after 5-8 days of
incubation, hemorrhagic diathesis,
hepatomegaly and circulatory
disturbance as shock.
Live attenuated vaccines have been
developed for yellow fever (strain 17D)
and Japanese encephalitis (JE; strain
SA14-14-2) viruses, and inactivated
vaccines have been developed for JE and
tick-borne encephalitis viruses. YF live
attenuated 17D vaccine are efficacious
and safe current vaccines been used to
immunize more than 300 million people.
Tetravalent live attenuated dengue
vaccines are undergoing clinical trials.
 Flaviviridae viruses.
This family contains about 70 RNA viruses,
the most important of which might be yellow
fever (YF). or dengue. Flaviviruses are
among the most important emerging viruses.
Most are arboviruses (arthropod-borne)
being transmitted by mosquitoes or ticks.
Many are spreading to new geographical
areas and causing increased numbers of
infections. Many RNA viruses have these
essential genes: pol, env and gag that are
major protein coding regions.
Viremia and immune responses.
Dengue virus is present in the blood of
infected patients for about 6 days after
which it is cleared by antibodies. Many
parts of the world do not have the
laboratory facilities required for virus
diagnosis or even the equipment and skill
for proper diagnosis of bacteria.
Nonetheless in some communities, the
political will to protect the public is not
evinced.
IgM antibody rises during acute illness.
Serological tests become positive by day 6.
IgM lasts 60-90 days, thus indicates recent
infection. However, IgM antibodies may
crossreact with other flaviviruses. In
primary dengue. IgG develops a few days
later than IgM antibody. Tests measuring
IgG antibody generally depend on paired
sera that show a difference in the course
of the infection, e. i., acute and
convalescent sera are compared.
Although secondary antibody
responses are broadly crossreactive,
there can be a higher response to
the primary infecting agent.
Distressing allergic reactions are
caused by crossreactions among the
4 dengue serotypes. Still, other
flaviviruses might be involved.
 Cultivation of the virus.

Animal viruses can be grown only in

cells, therefore the choices of hosts
are in vivo and in vitro mammalian
and insect hosts. Virus culture of
isolates will yield the needed data on
the virus and serotypes.
Many mammalian cells have long been
available for culturing various viruses,
whereas mosquito culture is more limited.
The 3 common cell lines are 1) C6/36 clone of
Aedes albopictus, 2) AP-61 line of A.
pseudoscutellanis and 3) the TRA-284 line of
Toxorhynchities amboinensis, C6/36 being the
most popular. The presence of virus is often
determined by fluorescent antibody (FA). The
monoclonal antibodies DEN 1 (1F1), DEN 2
(3H5), DEN 3 (8A1) and DEN 4 (1H10). Also,
an antigen capture ELISA test may be used.
 Vector control and surveillance.
Mosquito control involves only the vectors
Aedes aegypti and A. albopictus, the former
thoroughly domesticated. Vector control begins
with favorable political will and public health
financing, and can extend to the education of
schoolchildren. Community cooperation can be
the next step. The objective is the prevention of
vector breeding. Without a good garbage and
collection system, control will fail. Also,
without a good piped water system, people will
have to store water for household use, usually
in 200 liter drums.
Cleanup campaigns and clean neighborhoods
are keynotes for successful control and
depend on minimum health education. The
main breeding sites are softdrink plastic and
glass containers, and old discarded rubber
tires. A. aegypti breeds in and around houses.
Cleanup activity should reduce the necessity
for insecticide applications. Incriminating
mosquito breeding sites as propogating
diseases is the main target of community
communication.
Recycling is obviously beneficial,
especially via reducing the burning of
fuels, therefore available profit from
garbage collection requires reassessment
to provide maximum incentive for final
disposal of waste. Can the metal and even
glass in containers be transformed? Can
paper and plastics be recycled? The
profitable restoration of tires must lead to
the reduction of breeding sites.
 Insecticide applications.
In some districts, the larvicide Abate
(temephos) is the most important of 4
chemicals. Abate, often well recognized by
the public, is popular and sometimes delivered
by public health water trucks. Other chemicals
are the insect growth regulator IGR, another
IGR pyriproxyfen and methoprene. These
larvicides are effective with Aedes aegyptyi
and less so with mosquitoes that breed in
natural environments.
Space sprays can be applied to
neighborhoods as thermal fogs containing
a low concentration of organophosphate
(OP) life malathi-one, or pyrethroid
insecticide with diesel oil droplets as the
carrier. Doors and windows should be
open for the spray as so many mosquitoes
are inside houses. Spray cans with various
insecticides can help to control dengue,
yet at some expense.
Evaluations of vector densities
of Aedes aegypti and all other
mosquitoes should be continually
carried out. The use of ovitraps is
helpful, either with paddles for
egg-laying and counts, or sticky
ones that glue visiting mosquitoes
and other pests.
 Biological control.
Both parasitic bacteria and predatory
copepods are enemies that affect mosquito
population densities. Cyclopoids of the
genus Mesocyclops prey on the larvas of
several species of mosquitoes. Not to be
cleaned out, cyclopods require replacement
and care by the public managing the barrels.
Bacillus thuringiensis H-14 (BT) can control
Aedes aegypti. Granules and tablets of BT
mixtures are popular.
 Impregnated materials.
Insecticide impregnated curtains are
efficient for reducing mosquitoes in
houses. The natural repellents
dimethylphthalate (DMP) and
diethyltoluamide (DEET) at 35-50 %
are used as on clothing. Some repellents
on fabrics are efficient and long lasting,
e. g., pyrethroid permethrin. Nonetheless,
to repell rather than kill, seems to fail in
logic!
Some countries like Mexico have
DDT for use against malaria, but it
has not been incorporated into paint
or used much for impregnation.
OtherOP compounds include
diazinon, malathion, fenitrothion,
fenthion, dimethoate and dichlorvos.
The safety aspects of insecticides must
be well advertized.
Health communication
and public relations.
Control activities may contain research
results interesting for the target
audience. Good public communication
is influenced by the “knowledge,
attitude and practices” (KAP) studies
that have been made like questionaires.
Television notices are of course
effective, true also for health lessons to
schoolchildren.
Geographical Information Systems
(GIS).
The daily, monthly and annual weather cycles are
crucial factors in dengue epidemiology. In the
Americas, virus dispersal is influenced by the
Atlantic and the Eastern Pacific hurricane
centers. Only climate in North America is noted
here. Mexico has over six month of drought
through winter with convection current rains in
May, then cyclonic storms from July into
October. Climatic changes in one year or decade
to the next are not well studied.
Budgetary consideration.

Political will and public appreciation of

vector control measures are expected.
These measures likely include application
of larvicide or adulticide space sprays.
Much of this information is taken from
Key Issues. . ., WHO, 1995.
Health education should lead to public
particioation as in cleanup campaigns,
and then to political financing.
In order to estimate the costs of a control
program, the following information must
be collected:
a) The size of the geographical area to be
controlled,
b) the human population of the targeted area,
c) distribution, incidence and transmission,
d) length of time of transmission,
e) vector population density and seasonal
variation,
f) perferred larval habitats,
g) resting sites of adults, and
h) epidemiological pattern.
Dengue mainly affects children therefore most
expenses fall on the adults of the family. In
Thailand costs average US $ 128 per case. If the
patient has grade IV DHF/DSS, cost can be $
135. Private care costs about $ 400. Funeral costs
are about $ 400. Income loss per year was $
2,000. Epidemics in Thailand have cost $5-11
million (1994). Vector control can cost $ 2
million at $ 10/capita with 73.2 % for insecticides
and 17.5 % for wages of personnel. How do these
figures apply to your municipal situation? Are
West Nile virus infections carried by culicine
vectors complicating the situation?
 Summary.
Important points can now be summarized.
a) Aedes aegypti is fully domesticated so that its
biology is unlike that of other mosquitoes.
b) Containers and tires have to be reduced as
breeding sites via public appreciation of vector
control (try cleanup campaigns coupled with
schoolchild health education),
c) symptoms just like dengue transmission
should be advertized, and
d) the realistic calculation of risk and then the
possible need of a tetravalent vaccine should be
monitored.