DENGUE
Dr. Shubhangi Srivastava
Assistant Professor
Department of Community Medicine
Arthropod-borne
z
infection
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PROBLEM STATEMENT
Dengue fever (DF) and its severe forms — major
international public health concerns.
Past three decades – dramatic global increase.
Found – tropical and subtropical regions, more in urban
and semi-urban areas, and are now spreading to rural
areas.
Actual numbers of dengue cases – underreported and
misclassified.
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z PROBLEM STATEMENT –
INDIA
Dengue Fever – reported from most parts of the country
except those at high altitudes.
First case – Vellore Tamil Nadu – 1956
First major outbreak – 1963 in Kolkata.
Next major outbreak – Delhi in 1996.
Reporting made mandatory to ensure early preventive
measures in case of outbreak.
Endemic states – 35 states/UTs
Most affected states are Delhi, West Bengal, Kerala,
Tamil Nadu, Karnataka, Maharashtra, Rajasthan, Gujarat
and Haryana.
Largest number of cases and deaths due to
Dengue/DHF – 1996 and 2003.
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PROBLEM STATEMENT –
INDIA
Magnitude of the problem
140000 245
120000
220
100000
193
80000
129166 Deaths
60000 242 Cases
137 99913 58
40000 110 75808
169 50222
20000 28292 40571 36635
18860
0
2010 2011 2012 2013 2014 2015 2016 2017
(upto
Aug
20)
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z
PROBLEM STATEMENT –
INDIA
In 2017, till 20th Aug, the highest number of cases –
Kerala followed by Tamil Nadu, Karnataka, Andhra Pradesh
and Gujarat.
All the four serotypes i.e. dengue 1, 2, 3 and 4 have been
isolated in India but at present DENV-1 and DENV-2
serotypes are widespread in India.
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EPIDEMIOLOGY
Agent
(Dengue
Virus)
Host Environme
nt
(Humans) (Monsoons)
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EPIDEMIOLOGY
Agent Factors :
genus Flavivirus family Flaviviridae
Includes four serotypes – DenV - 1, DenV - 2, DenV - 3
and DenV - 4.
The Dengue virus is composed of single - stranded RNA.
Each serotype – Specific lifetime immunity and short -
term cross - immunity.
All serotypes can cause severe and fatal disease.
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EPIDEMIOLOGY
Genetic variations within serotypes – some are more virulent
or have greater epidemic potential.
A second infection by dengue serotype 2 or multiple infection
with different serotypes increases likelihood of suffering from
DHF/DSS due to immune enhancement mechanism.
Infection with one serotype provides life – long homologous
immunity.
First infection sensitizes the patient while second infection
with different serotypes produces immunological catastrophy.
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EPIDEMIOLOGY
Vector :
Aedes aegypti – main vector in India. It is a highly domesticated,
strongly anthropophilic, nervous feeder and is a discordant species.
Aedes albopictus – Another important vector, partly invades
peripheral areas of urban cities. It is an aggressive feeder and
concordant species.
Aedes aegypti is primarily a day time biter.
They rest indoors on various objects, in closets and other dark
places.
Outside, they rest where it is cool and shady.
EPIDEMIOLOGY
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Mosquito breeding –
any water – storage containers, such as desert coolers, flower vases,
coconut shells,
construction sites,
overhead uncovered or partially covered water tanks,
discarded buckets, tyres, utensils
large containers used for collecting rain water which are not emptied
and cleaned periodically.
Aedes mosquito can fly upto a limited distance of 400 meters
but can spread over vast distances mechanically in various
types of vehicles used by man.
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EPIDEMIOLOGY
Environmental Factors :
Outbreaks – most likely to occur in post – monsoon season.
High temperature(16-30 C) and high humidity(60-80%) during
these seasons prolongs its life span.
Spread results from several factors including human
behaviour , climate and movement of humans.
More in urban areas, can also occur in rural areas where the
environment is friendly for mosquito breeding like storage
water for cattle feeding and drinking, cement cisterns and
underground cemented water sumps.
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Breeds in containers in and around the house
Endophagic and endophilic
Even with 2 C increase in temeperature the extrinsic
incubation period is shortened and more infected
mosquitoes are available for a longer duration
Also the mosquitoes will bite more frequently due to
dehydration increasing man mosquito contact
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EPIDEMIOLOGY
Transmission :
Becomes infective by feeding on a patient
from day before onset to 5th day (viraemia
stage) of illness
Transmitted by – infected female Aedes aegypti.
Mosquitoes acquire virus – feeding on an infected person.
Extrinsic incubation period of 8 to 10 days – an infected
mosquito can transmit virus for rest of its life.
Trans - ovarian transmission of the Dengue virus in mosquitoes
maintains the virus in nature.
Humans – main host of the virus, monkeys may be infected.
The virus circulates in the blood of infected humans for two to
seven days.
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DENGUE IN THE COMMUNITY
Initiation and maintenance of an
epidemic –
Strain of the virus, which may influence the
magnitude and duration of the viraemia in
humans
Density, behaviour and vectorial capacity of
the vector population
Susceptibility of the human population (both
genetic factors and pre-existing immune
profile)
Introduction of the virus into a receptive
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DENGUE IN THE COMMUNITY
Pyramid phenomenon or Iceberg
Clusters of cases have been reported in particular
households or neighbourhoods – feeding behaviour of
vector.
The population affected varies in each outbreak.
Actual estimates can be made by obtaining
clinical/subclinical ratios during epidemic time
In a well-defined epidemic study, 20% to 50% of the
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population was found affected.
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DF/DHF
z
Dengue
shock
syndrome
Dengue
Haemorrha
gic fever
Dengue
fever
Symptomless
cases
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DENGUE IN THE COMMUNITY
Serotype that produce secondary infection & serotype
sequence – important to ascertain severity of the disease.
Studies in Thailand have revealed that the DENV-1/ DENV-2
sequence of infection was associated with a 500 fold risk of
DHF.
For the DENV-1/DENV-2 sequence the risk was 500
fold,DENV-3/DENV-2 sequence the risk was 150-fold, and a
DENV-4/DENV-2 sequence had a 50-fold risk of DHF.
There is no time-limit to sensitization after a primary
infection.
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HIGH RISK PEOPLE
Infants and elderly
Obesity
Pregnancy
Peptic ulcer disease
Women who are in menstruation or have abnormal bleeding
Haemolytic disease such as G–6PD, thalassemia and other
haemoglobinopathies
Congenital heart disease
Chronic diseases such as diabetes, hypertension, asthma, ischaemic
heart disease, chronic renal failure, liver cirrhosis
Patients on steroid or NSAID treatment
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CLINICAL FEATURES
Incubation period – usually 5 - 6 days, but may vary from
3 to 10 days.
It can result in four different clinical syndromes
Undifferentiated fever
Classic Dengue fever
Dengue Haemorrhagic fever
(DHF)
Dengue Shock syndrome
(DSS)
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Manifestations of Dengue virus
infection
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CLINICAL FEATURES
Undifferentiated Fever :
Most common manifestation of Dengue.
Primary dengue infection may develop a simple fever
indistuinguishable from other viral infection
Almost 90% – asymptomatic or only mildly symptomatic.
Upper respiratory and gastroinstestinal symptoms are
common
Maculopapular rash may accompany the fever
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CLINICAL FEATURES
Classical dengue fever:
Sudden onset, with chills and high fever,
intense headache, muscle and joint pains,
which prevent all movements.
Within 24 hours – retroorbital pain, particularly
on eye movements or eye pressure and
photophobia.
Other common symptoms – extreme weakness,
anorexia, constipation, altered taste sensation,
colicky pain and abdominal tenderness,
dragging pain in inguinal region, sore throat.
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CLINICAL FEATURES
Fever – between 39°C and 40°C. Fever is typically
but not inevitably followed by a remission of a few
hours to 2 days (biphasic curve).
Skin eruptions – 80% cases during remission or
second febrile phase.
Rash – 1st half – flushing, mottling or fleeting pin—
point eruptions on the face, neck and chest
Conspicuous rash, maculopapular or scarlatiniform
on 3rd or 4th day – Accompanied by itching &
hyperaesthesia. Followed by desquamation.
Case fatality – low.
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CLINICAL FEATURES
Source – WHO 2009 Dengue, Guidelines for diagnosis, prevention and
treatment
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Dengue hemorrhagic fever
Febrile phase –
After incubation period – high fever accompanied by
facial flushing and headache.
Anorexia, vomiting, epigastric discomfort, tenderness at
the right costal margin and generalized abdominal pain.
First few days – resembles classical DF, but
maculopapular rash usually rubelliform type, is less
common.
Febrile convulsions may occur particularly in infants.
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CLINICAL FEATURES
The major pathophysiologic changes – plasma leakage
and abnormal haemostasis
Manifested by a rising haematocrit value and moderate
to marked thrombocytopenia.
Positive torniquet test – most common.
The test is positive when 10 or more petechiae per 1 inch
square are observed.
In DHF – definite positive with 20 petechiae or more.
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CLINICAL FEATURES
Critical phase:
Starts with drop in temperature (37.5–38oC) – increase in
capillary permeability in parallel with increasing
haematocrit levels.
Progressive leukopenia followed by a rapid decrease in
platelet count.
Period of clinically significant plasma leakage usually
lasts 24–48 hours.
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CLINICAL FEATURES
Progressive
leukopenia
increase in
No increase in
capillary
capillary
permeability -
permeability
worsens
Abdominal
Chest X-ray Improves
ultrasound
Degree of
Volume of fluid
plasma
therapy
leakage
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CLINICAL FEATURES
Shock occurs when a critical volume of plasma is lost.
Often preceded by warning signs.
Prolonged shock leads to consequent organ hypoperfusion
results in progressive organ impairment, metabolic acidosis
and disseminated intravascular coagulation.
Instead of leukopenia, the total white cell count may increase
in patients with severe bleeding.
Severe hepatitis, encephalitis or myocarditis and/or severe
bleeding may also develop without obvious plasma leakage or
shock.
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CLINICAL FEATURES
Recovery phase:
If patient survives critical phase, a gradual reabsorption of
extravascular compartment fluid takes place in next 48–72
hours.
General well – being improves, appetite returns, gastrointestinal
symptoms abate, haemodynamic status stabilizes and diuresis.
A rash of “isles of white in the sea of red”.
Some may experience generalized pruritus.
Bradycardia and electrocardiographic changes can be seen.
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CLINICAL FEATURES
The haematocrit stabilizes or may decrease.
White blood cell count usually starts to rise soon after
defervescence but recovery of platelet count is typically
later than that of white blood cell count.
Excessive intravenous fluids – Respiratory distress from
massive pleural effusion and ascites.
Associated with pulmonary oedema or congestive heart
failure.
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CLINICAL FEATURES
Severe dengue:
It is defined by one or more of the following:
plasma leakage that may lead to shock (dengue shock) and/or
fluid accumulation, with or without respiratory distress, and/or
severe bleeding, and/or
severe organ impairment.
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CLINICAL FEATURES
Patients in dengue shock – conscious and lucid.
There is decompensation and both pressures disappear
abruptly.
Prolonged hypotensive shock and hypoxia may lead to
multi-organ failure and an extremely difficult clinical
course.
35 The patient is considered to have shock if the
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pulse pressure is <20 mm Hg in children or
he/she has signs of poor capillary perfusion
(cold extremities, delaye capillary refill, or
rapid pulse rate).
In adults, the pulse pressure of < 20 mm Hg
may indicate a more severe shock.
Hypotension is usually associated with
prolonged shock which is often complicated
by major bleeding.
Patients with severe dengue may have
coagulation abnormalities, but these are
usually not sufficient to cause major bleeding
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When major bleeding does occur, it is
almost always associated with profound
shock since this, in combination with
thrombocytopenia, hypoxia and acidosis,
can lead to multiple organ failure and
advanced disseminated intravascular
coagulation.
Massive bleeding may occur without
prolonged shock in instances when
acetylsalicylic acid (aspirin), ibuprofen or
corticosteroids have been taken
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Unusual manifestations, including acute liver
failure and encephalopathy, may be present,
even in the absence of severe plasma
leakage or shock.
Cardiomyopathy and encephalitis are also
reported in a few dengue cases.
Most deaths from dengue occur in patients
with profound shock, particularly if the
situation is complicated by fluid overload.
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CLINICAL FEATURES
The patient – shock if pulse pressure is ≤ 20 mm Hg in
children or he/she has signs of poor capillary perfusion
(cold extremities, delayed capillary refill, or rapid pulse
rate).
PP - ≤ 20 mm Hg - More severe shock in adults.
Hypotension with prolonged shock – often complicated by
major bleeding.
It also has thrombocytopaenia, hypoxia and acidosis, can
lead to multiple organ failure and advanced disseminated
intravascular coagulation.
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DIAGNOSIS
CLINICAL DIAGNOSIS- Probable diagnosis
Acute febrile illness with two or more of the
following;
headache
retro-orbital pain
myalgia
arthralgia/bone pain
rash
Haemorrhagic manifestations
Leucopenia (wbc 5 5000 cells/mm3)
Thrombocytopenia (platelet count <150,000
cells/mm3),
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At least one of the following :
supportive serology on single
serum sample: positive
haemagglutination inhibition test,
comparable IgG titre, or testing
positive in IgM antibody
occurrence at the same location
and time as confirmed cases of
dengue fever.
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DIAGNOSIS
Confirmed diagnosis
Probable case with at least one of the
following :
isolation of dengue virus from autopsy samples,
serum or CSF
fourfold or greater increase in serum lgG or
increase in IgM antibody specific to dengue virus.
detection of dengue virus or antigen in tissue,
serum or cerebrospinal fluid by
immunohistochemistry, immunofluorescence or
ELISA.
detection of dengue virus genomic sequences by
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DIAGNOSIS
Dengue haemorrhagic fever
All of the following :
acute onset of fever of two to seven days
duration.
haemorrhagic manifestations
platelet count 100,000 cells/mm3
objective evidence of plasma leakage due to
increased vascular permeability shown by any
of the following :
Rising haematocrit/haemoconcentration 20%
from baseline
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Dengue shock
z
syndrome
Tachycardia, cool extremities, delayed capillary
refill, weak pulse, lethargy or restlessness,
which may be a sign that brain perfusion is
reduced
Pulse pressure<20 mmHg with increased
diastolic pressure, e.g. 100/80 mmHg
Hypotension by age, defined as systolic
pressure<80 mmHg for those aged < 5years or
80 to 90 mmHg for older children and adults
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DIAGNOSIS
Dengue shock syndrome
Criteria for dengue haemorrhagic fever with signs of
shock including
tachycardia, cool extremities, delayed capillary refill, weak pulse,
lethargy or restlessness, which may be sign of reduced brain
perfusion.
pulse pressure 20 mmHg with increased diastolic pressure, e.g.
100/80 mmHg.
hypotension by age.
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LABORATORY DIAGNOSIS
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TREATMENT
Grading of the severity of dengue infection
To decide where to treat the patient, it is important to
classify the severity of dengue infection.
Guidelines for treatment
A full blood count should be done at the first visit.
A haematocrit test in early febrile phase establishes
patient's own baseline haematocrit.
A rapidly decreasing platelet count in parallel with a
rising haematocrit compared to baseline is suggestive
of progress to the plasma leakage/critical phase.
In absence of patients baseline, age specific population
haematocrit levels can be used.
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TREATMENT
Management of dengue fever
These are patients who are able to tolerate
adequate volumes of oral fluids and pass urine at
least once every six hours, and do not have any
of the warning signs.
There is no specific anti-viral treatment for
dengue illness.
Patients are told to adhere to following action
plan :
Encourage intake of oral rehydration solution (ORS),
fruit juice and other fluids containing electrolytes and
sugar
Give paracetamol for high fever. The interval of
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TREATMENT
Tepid sponge if the patient still has high fever.
Do not give acetylsalicylic acid (aspirin), ibuprofen or other
NSAIDs as these drugs may aggravate bleeding or gastritis.
Instruct the care-givers that patient should be brought to
hospital immediately if any of following occur –
no clinical improvement, deterioration around the time of
defervescence, severe abdominal pain, persistent vomiting,
cold and clammy extremities, lethargy or irritability/
restlessness, bleeding, not passing urine for more than 4-6
hours.
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TREATMENT
Management of DHF (Febrile Phase)
Similar to that of DF. Paracetamol is recommended to keep
the temperature below 39°C.
Copious amount of fluid should be given orally, such as
oral rehydration solution (ORS), and/or fruit juices
IV fluid may be administered if the patient is vomiting
persistently or refusing to feed.
Patients should be closely monitored for the initial signs of
shock.
Serial haematorcrit determinations are essential guide for
treatment, since they reflect the degree of plasma leakage
and need for intravenous administration of fluids.
Haematocrit should be determined daily from the third day
until the temperature has remained normal.
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z TREATMENT
Management of DHF grade 1 and 2
Volume replacement algorithm for patients with moderate dengue fever
(DHF Grades I & II )
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TREATMENT
Management of DHF grade 3 and 4
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TREATMENT
Indications of red cell transfusion
Loss of blood (overt blood) - 10 per cent or more of total blood
volume - preferably give whole blood.
Refractory shock despite adequate fluid administration and
declining haematocrit.
Replacement volume should be 10 ml/kg body weight at a time
and coagulogram should be done.
If fluid overload is present packed cells are to be given.
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TREATMENT
Indications of platelet transfusion
Prophylactic platelet transfusion may be given at level of <
10,000/cu.mm.
Prolonged shock; with coagulopathy and abnormal coagulogram.
In case of systemic massive bleeding, platelet transfusion may be
needed in addition to red cell transfusion.
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TREATMENT
Criteria for discharge
Absence of fever for atleast 24 hours without the use of anti-
pyretic drugs.
Return of appetite.
Visible improvement clinically.
Good output of urine.
Minimum of 2-3 days after recovery from shock.
No respiratory distress from pleural effusion or ascites.
Platelet count > 50,000/cu.mm.
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PREVENTION
Mosquito control
Other measures
Vaccines
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MOSQUITO CONTROL
ANTI-LARVAL MEASURES
Environmental control
Chemical control
Biological control.
ANTI-ADULT MEASURES
Residual sprays
Space sprays
Genetic control.
PROTECTION AGAINST MOSQUITO BITES
Mosquito net
Screening
Repellents.
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OTHER MEASURES
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VACCINE
CYD-TDV or DENGAVAXIA –
prophylactic, tetravalent, live attenuated viral vaccine
developed by Sanofi Pasteur.
Vaccination schedule – 3 injections of 0.5 ml
administered at 6-month intervals.
Used for prevention of illness caused by dengue virus
serotypes 1, 2, 3, and 4 in individuals 9–45 years or
9–60 years of age, living in dengue endemic areas.
Available in a single-dose vial or in a multidose
(5-dose) vial.
It is a freeze-dried product to be reconstituted
before injection with sterile solution of sodium
chloride.
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VACCINE
After reconstitution, the 0.5 mL dose is to be
administered by the subcutaneous route.
Contains no preservatives or adjuvant.
The shelf-life is 36 months when stored between
2 °C and 8°C.
After reconstitution, the vaccine must be kept at
between 2 °C and 8 °C and protected from light.
Should be discarded within 6 hours of
opening/reconstitution or at the end of a
vaccination session, whichever comes first.
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z Other measures
Isolation of the patient under bed-nets during the
first few days; individual protection against
mosquitoes.
The personal prophylactic measures are wearing of
full sleeves shirts and full pants; use of mosquito
repellent creams, liquids, coils, mats etc.; use of
bed-nets for sleeping infants and young children
during day time to prevent mosquito bite.
The environmental measurements are detection
and elimination of mosquito breeding places,
management of roof tops, porticos and sunshades,
proper covering of stored water, observation of
weekly dry day.
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z GLOBAL STRATEGY FOR DENGUE
PREVENTION AND CONTROL 2012 –2020
Dengue is a global threat that requires a global
reaction.
The global strategy promotes co-ordination and
collaboration among multisectoral partners on
integrated vector management approach and
sustained control measures at all levels.
The goals are :
to reduce dengue mortality by at least 50 per cent by
2020
to reduce dengue morbidity by at least 25 per cent by
2020
to estimate the true burden of the disease by 2015.
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