Dengue Paul R. Earl Facultad de Ciencias Biol

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DenguePaul R. EarlFacultad de Ciencias
BiológicasUniversidad Autónoma de Nuevo LeónSan
Nicolás de los Garza, Nl, Mexico
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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.
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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.
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Dengue can be prevented by 1) elimination of
mosquito breeding places, 2) prevention of
mosquito bites and3) vaccination of all persons
against all 4 serotypes, DEN 1-4.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.

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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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!
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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.
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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.
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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.
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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.
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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.
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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?
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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.