PROJECT WORK REPORT

A Review Article Of dengue fever

Submitted To Gujarat Technological University

IN
B. PHARMACY
SEMESTER-VIII

BY
NAME OF STUDENT: MEET PANASARA
ENROLLMENT NO:172500290032

SHREE H.N.SHUKLA INSTITUTE OF PHARMACEUTICAL

EDUCATION AND RESEARCH
B/H MARKETING YARD,
NR. LALPARI LAKE,
AMARGADH-BHICHARI, RAJKOT, GUJARAT, INDIA
 Declaration
I hereby declare that thesis entitled “A Review Article Of dengue
fever” is a bonafide and genuine carried out by me. The results or
observational data presented in this report are original.

26/04/2021 Meet panasara

Place: Rajkot
172500290032

Shree H.N.Shukla Institute Of

Pharmaceutical Education And Research

B/H Marketing Yard,

Nr. Lalpari Lake,

Amargadh-Bhichari,Rajkot, Gujarat, India

 ACKNOWLEDGEMENT
“Knowledge is in the end based on acknowledgement.”
I warp up this project; I take this opportunity to express my thanks
to all who helped to complete the task.
I take this opportunity to express my deep sense of gratitude to my
guide MISS.MEENA SINHAR, M.PHARM., assistant professor of
shree h.n.shukla institute of pharmaceutical education and research, for
her guidance, valuable suggestions and liberal encouragement to
complete this work successfully entitled “A REVIEW ARTICLE OF
DENGUE FEVER”
It’s my privilege and honor to thank DR.DHARA
CHAVDA,M.PHARM,Ph.D., principal, shree h.n.shukla institute of
pharmaceutical education and research, for providing all the necessary
facilities to do this project work.

INDEX:

SR.NO DESCRIPTION
1. Abstract
2. Key words
3. Introduction
4. Etiology
5. Epidemiology
6. Pathophysiology
7. Transmission
8. Manifestations
9. Diagnosis
10. Treatment
11. Prevention
12. Conclusion

Abstrac
Dengue fever is a disease caused by a family of viruses transmitted by
mosquitoes. Dengue virus (DENV), a member of the Flaviviridae family,
causes the most widespread mosquito-borne viral infection in humans
around the world today. Dengue can affect anyone but tends to be more
severe in people with compromised immune systems. Dengue
hemorrhagic fever is a more severe form of a viral illness. Symptoms
include headache, fever, rash, and evidence of bleeding (hemorrhage) in
the body. This form of dengue fever can be life-threatening and can
progress to the most severe form of the illness, dengue shock syndrome.
This chapter reviews the etiology, epidemiology, diagnosis,
pathophysiology, transmissions, manifestations, diagnosis, treatment, and
prevention of dengue.

Keywords;
Dengue,
Etiology,
Epidemiology,
pathophysiology
1. Introduction
Dengue fever is a mosquito-borne viral infection which has a sudden onset
that follows symptoms such as headache, nausea, weakness, intense
muscle and joint pain, swelling of lymph nodes (lymphadenopathy), and
rashes on the skin. Many symptoms of dengue fever include gingivitis,
sharp pain in the eyes, and swollen palms and soles.

Dengue can affect any person but appears to be more serious in

immunocompromised people. Because it is caused by one of the five
dengue virus serotypes, it is possible to have dengue fever multiple times.
Nonetheless, a dengue attack provides lifelong immunity to the specific
viral serotype to which the patient has been exposed. This disease may
also be called “breakbone fever” or “dandy fever.”

This dengue fever may become more serious and then named as dengue
hemorrhagic fever and dengue shock syndrome. Dengue hemorrhagic
fever is a more severe form in which hemorrhages occurs in the body. It
is a life-threatening condition, and it may progress to the most critical
form called dengue shock syndrome.

2. Etiology
Dengue virus (DENV) is a single-stranded, positive-sense RNA virus in
the Flaviviridae family and the Flavivirus genus. When viewed under the
transmission electron micrograph, the virions appear as a bunch of black
spots. Yellow fever virus, West Nile virus, St. Louis encephalitis virus,
Japanese encephalitis virus, tick-borne encephalitis virus, Kyasanur
Forest disease virus, and Omsk hemorrhagic fever virus belong to this
family, and majority of them is transmitted by arthropods (mosquitoes or
ticks).
Approximately 11,000 nucleotide bases were present in the dengue
genome, which codes for a single polyprotein. It is made up of three
structural protein molecules that constitute the virus particle and seven
nonstructural proteins (NS1, NS2a, NS2b, NS3, NS4a, NS4b, and NS5)
which are required for viral replication [3, 4]. The five strains of the virus
(DENV-1, DENV-2, DENV-3, DENV-4, and DENV-5) are referred to as
serotypes because they vary in serum reactivity.
The main cause of dengue fever is an infected mosquito bite , and besides
it, it may be accidentally acquired after vertical transmission, especially
in near-term pregnant women through the placenta, infected blood
products, through organ transplantation, and even after needle stick
injury.

3. Epidemiology
Awareness about the terrestrial spread and impact of dengue is relevant
for assessing its relation to worldwide morbidity and mortality and
knowing how to utilize the available resources for controlling the dengue
globally.

Only nine countries had suffered major epidemics of dengue, before 1970.
Currently it is common in most of the regions of the WHO. The Americas,
South East Asia, and Western Pacific areas are the most severely affected,
with Asia responsible for around 70% of the global disease burden.
Throughout the recent decades, the prevalence of dengue has significantly
elevated around the globe. The vast majority of cases are asymptomatic
or mild and self-managed, and therefore the actual number of dengue
cases is underreported. Many cases are also misdiagnosed as other febrile
disorders.
One report indicates 390 million dengue virus infections per year, of
which 96 million occur clinically (with any disease severity). The report
on dengue prevalence reports that 3.9 billion people are at risk of infection
with dengue viruses. Despite the risk of infection in 128 countries, 70%
of the real burden is from Asia.

The number of dengue cases recorded to WHO has risen ~6 fold, from
<0.5 million in 2010 to more than 3.34 million in 2016. The year 2016
was marked by massive dengue outbreaks worldwide. A major reduction
in the number of dengue cases in the Americas was reported in 2017, from
2,177,171 cases in 2016 to 584,263 cases in 2017. It reflects a drop of
73%. Following a drop in the number of cases in 2017–2018, a sharp
increase in cases is reported in 2019. Cases have increased in Australia,
Cambodia, China, Lao PDR, Malaysia, the Philippines, Singapore, and
Vietnam. An estimated 500,000 people with severe dengue require
hospitalization every year, and an estimated 2.5% of cases are fatal each
year. Nevertheless, several countries have lowered the case fatality rate to
less than 1%, and internationally, there has been a decline in case of
fatality between 2010 and 2016, with a significant improvement in case
management through country-level capacity building. The only continent
that has not witnessed dengue transmission is Antarctica.
The global burden of dengue is formidable and is a growing challenge for
public health officials and policymakers. Success in addressing this
growing global threat depends, in part, on strengthening the evidence base
on which planning control decisions and their impact are assessed. It is
hoped that this assessment of the distribution and burden of contemporary
dengue risk will help to advance this objective.
4. Pathophysiology
The pathophysiology of DENV and the immune response of the host are
not fully understood. Primary manifestations of disease include capillary
leak syndrome, hemorrhagic tendencies, and leukopenia. It is known that
the major viral envelope of glycoprotein in the virus helps to bind the host
cells, followed by viral replication. Data suggest that monocytes are the
primary target. Infected monocytes induce the production of interferon-a
(IFN-a) and IFN-b. Envelope, precursor membrane protein (pre-M), and
nonstructural protein 1 (NS1) are the major DENV proteins targeted by
antibodies as part of the host immune response. Studies have shown that
DENV-specific CD4+ and CD8+ T lymphocytes attack infected cells and
release IFN-g, tumor necrosis factor-a (TNF-a), and lymphotoxin.
Primary infection induces a lifetime immunity of the individual to that
particular serotype, but not to secondary infection by another serotype.

5. Transmission
Dengue virus is the most common mosquito-borne infection in humans
all over the world. It belongs to the family Flaviviridae, which contains
more than 70 viruses, in which DENV is transmitted by the Aedes
aegypti and Aedes albopictus mosquitoes.

Dengue virus is spread primarily by Aedes mosquitoes, in particular Aedes

aegypti. These mosquitoes usually live between 35°N and 35°S below an
altitude of 1000 m . They usually bite especially in the early morning and
in the evening. Certain Aedes disease-borne species include Aedes
albopictus, Aedes scutellaris, and Aedes polynesiensis. Human beings are
the primary hosts of this virus, arousing even nonhuman primates. An
infection may be obtained through a single bite. A female mosquito that
consumes an infected person’s blood (within a febrile, viremic span of 2
to 12 days) becomes infected with the virus in its intestine. The virus then
spread into other tissues, including the salivary glands of the mosquito,
approximately after a period of 8–10 days and is subsequently released
into its saliva. When it bites the other person, the virus is transmitted
through its saliva to that person. The virus does not cause any harm to the
mosquito. Aedes aegypti is a main concern as it prefers to lay its eggs in
containers of freshwater and stay close to humans. Infected blood
products and organ donation can also cause dengue. Even in countries like
Singapore, the incidence is approximately 1.6 to 6 in 10,000 transfusions.
The vertical transmission (from mother to child) during pregnancy or at
birth is also documented. Other person-to-person forms of transmission
have also been reported, but are very rare. Dengue’s genetic variants are
regionally specific, indicating that the creation of new territories is
relatively rare, despite the fact that dengue has appeared in new regions
in recent decades .

The virus
DENV is a small single-stranded RNA virus consisting of five different
serotypes (DENV-1 to DENV-5). The virus particle is spherical in shape
with a diameter of 50 nm. The genome is divided into three structural
proteins and seven nonstructural proteins (NS) by the host and viral
proteases.

Within each serotype, distinct genotypes or lineages (viruses closely

related in nucleotide sequence) have been identified, demonstrating the
substantial genetic variability in dengue serotypes. However, purifying
selection continues to be a dominant theme in the evolution of dengue
viruses, so only viruses that are “fit” for both humans and vectors are
retained. Between these, severe secondary dengue infections are often
associated with “European” genotypes DENV-2 and DENV-3. The
human hosts have established intra-host viral diversity (quasi-species).

The vectors
Different dengue virus serotypes are transmitted to humans through the
bites of infected Aedes mosquitoes, mainly Aedes aegypti. This mosquito
is a tropical and subtropical species widely distributed around the world,
mostly between 35°N and 35°S latitudes. Such geographical limits
correspond roughly to the 10°C winter isotherm. Aedes aegypti was
located as far north as 45°N, but in warmer months, these invasions took
place, and the mosquitoes did not survive the winter months. Aedes
aegypti is also relatively uncommon over 1000 m, due to lower
temperatures. The embryonic stages are found in water-filled settings,
mostly in artificial containers that are closely linked to human dwellings,
and often inside. Research suggests that mostly female Aedes aegypti may
spend their lives in or around the homes where the adults emerge. It means
people are spreading the virus quickly within and between populations,
rather than mosquitoes. Aedes albopictus, Aedes polynesiensis, and
several species of Aedes scutellaris were also attributed to outbreaks of
the dengue. Each of these species has a specific ecological, behavioral,
and geographical distribution. Aedes albopictus has spread from Asia to
Africa, Americas, and Europe in recent decades, aided particular by
international trade in used tires, where eggs are deposited as they contain
rainwater. Eggs can remain viable for many months, in the absence of
water.

The host
After an incubation period of 4–10 days, infection with any of the four
virus serotypes can cause a wide range of illnesses, although most
infections are asymptomatic or subclinical. Primary infection is thought
to cause long-term defensive immunity to serotype infections. Around 2–
3 months of primary infection, but without long-term cross-protective
immunity, individuals suffering from infection are protected from clinical
illness with a specific serotype.

Personal risk factors influence the severity of the disease and also include
secondary infections (bronchial asthma, sickle cell anemia, and diabetes
mellitus), age, race, and potentially chronic diseases. In particular, young
children may be less able to compensate for capillary leakage than adults
and are thus at a higher risk of dengue shock.
Seroepidemiological reports conducted in Cuba and Thailand strongly
support the position of secondary heterotypic infection as a risk factor for
severe dengue, although there is little evidence of serious primary
infection cases. Also, the time interval between infections and the specific
viral infection sequence may be significant. For example, a higher fatality
rate was observed in Cuba when DEN2 infection followed DEN-1
infection at an interval of 20 years compared to 4 years. Severe dengue is
also commonly seen in infants born to dengue-infected mothers.
Antibody-dependent enhancement (ADE) of the infection has been
hypothesized as a mechanism to explain severe dengue in the course of
secondary infection and in infants with primary infections. In this model,
non-neutralizing, cross-reactive antibodies produced during primary
infection or acquired passively at birth bind to epitopes on the surface of
the heterologous infective virus and promote the entry of the virus into
Fc-bearing cells. The increased number of infected cells is expected to
result in increased viral load and robust host immune response activation
including inflammatory cytokines and mediators, some of which may
contribute to capillary leakage. Cross-reactive memory T cells are also
rapidly triggered during secondary infection, proliferate, release
cytokines, and die of apoptosis in a manner that usually correlates with
overall disease severity. Host genetic determinants may have an effect on
the clinical outcome of infection, although most studies have not been
able to address this problem adequately. Studies in the American region
indicate that the levels of extreme dengue in individuals of African
descent are lower than in other ethnic groups.

Recent data suggest that endothelial cell activation could mediate plasma
leakage. Plasma leakage is believed to be associated with functional
effects on endothelial cells, rather than harmful ones. Endothelial cell
dysfunction may also be associated with the activation of infected
monocytes and T cells, the complement system, and the production of
mediators, monokines, cytokines, and soluble receptors.

Thrombocytopenia may be associated with alterations in

megacaryocytopoiesis due to human hematopoietic cell infection and
impaired progenitor cell growth, resulting in platelet dysfunction
(activation and aggregation of platelets), increased destruction, or
consumption (peripheral sequestration and consumption). Hemorrhage
may result from thrombocytopenia and related platelet dysfunction or
intravascular coagulation. In short, a transient and reversible imbalance of
inflammatory mediators, cytokine, and chemokine occurs during severe
dengue times, probably due to high early viral loads, leading to vascular
endothelial cell dysfunction, hemocoagulation disorders, and then plasma
leakage, shock, and bleeding.

6. Manifestations
One of three clinical forms can be used in humans, such as dengue fever
(DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome
(DSS).

Approximately one-half of the DENV infections are asymptomatic, and

some are undifferentiated (in which the patient develops fever and mild
symptoms, but the source of the infection is not diagnosed as DENV). The
three clinical forms of the disease vary in the severity of their symptoms,
with the influenza-like DF being the least severe and the DSS being the
most severe. In most cases, mild febrile DF is not fatal; however,
infections that develop into DHF or DSS may be life-threatening and
cause death in many cases. Patients with DHF and DSS were found to
have virus titers 100- to 1000-fold higher than those with DF from the
initial stage of infection. Overall, DENV infection has been found to be
more severe in children than adults.

Based on the outcome of several studies, the WHO has developed a new
dengue classification. It differentiates dengue cases into cases with or
without warning signs and serious cases of dengue.

Usually, signs begin to appear after an incubation period of 3–10 days.

The severity of clinical presentations ranges from mild symptoms to
extreme life-threatening symptoms for dengue hemorrhagic fever and
dengue shock syndrome. Predicting the progression of mild signs to
severe DHF/DSS remains a challenge due to unspecific clinical
presentation and incomplete understanding of disease pathophysiology
and its underlying molecular mechanisms.

The early signs of the disease are nonspecific. According to WHO, DF is

characterized by febrile episodes (≥40°C for 2–7 days) often associated
with rash, nausea, vomiting, and headache. Even though the disease
affects all ages of people from infant to adulthood, epidemiological data
showed that children tend to control this disease better than adults. The
severity of the above symptoms and the emergence of other symptoms,
such as abdominal pain, mucosal bleeding, and lethargy and restlessness,
can be seen after 3–7 days. Laboratory examination of mild dengue fever
cases usually reveals elevated leukocyte counts and a small increase in
hepatic aminotransferase activity. The emergence of these symptoms is a
warning sign of disease progression to severe form (DHF/DSS) if
therapeutic action is not undertaken. At this level, clinical intervention
and continuous surveillance are necessary to prevent vascular leakage,
especially in the endemic region.

Extreme dengue infection can be due to any of the four recognized DENV
1–4 serotypes. The likelihood of developing DHF/DSS is high in patients
who have had dengue infection with heterogeneous serotype in the past,
with approximately 5–10% of patients developing extreme DHF/DSS that
can be fatal unless treated promptly.

This type evolves at a late stage of DF, where patients will experience a
defervescent process characterized by a sudden drop in body temperature.
This phase is also characterized by severe bleeding, especially from the
gastrointestinal tract (black, tarry stool) and thrombocytopenia
(<50,000/mm3), which may affect up to 50% of DHF cases. Ironically,
there was a negative correlation between the frequency of DHF and the
number of platelets in the blood. The exact mechanism of this association
is yet to be identified. Decreased platelet counts and loss of function
contribute to vascular fragility, increasing the risk of hemorrhage and
plasma leakage59. It has been proposed that DENV replicates rapidly in
platelets during the acute phase of infection, as this is very important to
the survival and dissemination of the virus. The existence of other signs
such as retro-orbital pain, maculopapular rash, petechiae, or nose or gum
bleeding may help to make a definitive diagnosis of DF. Subsistence in
systolic pressure and hypotension can result in profound shock, known as
dengue shock syndrome. Long-term DSS duration can predispose to
additional complications such as severe bleeding, diffuse intravascular
coagulopathy (DIC), respiratory failure, multiorgan failure, and
infrequently encephalopathy leading to death. It was estimated that DHF-
related case fatality could exceed 15% of all cases, but proper medical
treatment and symptomatic management could minimize the mortality
rate to less than 1%.

Signs and symptoms depending on the stage of the disease reflect the
dengue fever. People with dengue virus normally become asymptomatic
(80%) or have mild symptoms such as uncomplicated fever. 5 % of the
people have more severe illness and, in a small proportion of cases (<1%),
are life-threatening and cause death despite care. The incubation period
(time between exposure and onset of symptoms) ranges from 3 to 14 days,
but most of the time is 4 to 7 days. Children are more likely to have
atypical symptoms, often with common cold or gastroenteritis (vomiting
and diarrhea)-like symptoms.

The characteristic symptoms of dengue are sudden fever, headache

(typically behind the eyes), muscle and joint pain, and rash. The course of
infection is divided into three phases: febrile, serious, and recovery. The
febrile phase includes high fever, possibly over 40°C (104°F) and is
associated with severe pain and headache; this period usually lasts 2–
7 days. Vomiting and rash will be there along with flushed skin. In some
cases, the illness is progressing to a serious stage as the fever clears. This
process is characterized by major, diffuse plasma leakage usually lasting
1–2 days. Organ dysfunction and severe bleeding, usually from the
gastrointestinal tract, may also occur. Shock (dengue shock syndrome)
and hemorrhage (dengue hemorrhagic fever) occur in less than 5% of all
dengue cases. This serious phase is more common among children and
young adults. The recovery phase is followed by the resorption of the
leaked fluid into the bloodstream over a duration of 2–3 days. The change
is often startling and can be followed by serious pruritus and bradycardia.
The rash can occur, with either a maculopapular or a vasculitic appearance
accompanied by desquamation. A fluid-overloaded condition can occur
during this stage, in rare cases.

Dengue also affects a variety of other body systems, either in isolation or

along with typical dengue symptoms. Decreased sensitivity occurs in 0.5–
6% of severe cases, due to encephalitis or, indirectly, to compromised
vital organs (e.g., hepatic encephalopathy). Other neurological disorders
similar to dengue, such as transverse myelitis and Guillain-Barré
syndrome, have been identified. Myocarditis and acute liver failure are
among the most rare complications.

7. Diagnosis
Signs and symptoms of dengue fever are similar to some other illnesses,
such as typhoid fever or malaria, which can sometimes hinder the
likelihood of a timely and correct diagnosis. It may be diagnosed by the
patient’s signs and symptoms, patient’s medical history, and testing blood
samples (preliminary by platelet count, followed by ELISA, HI assay, and
RT-PCR).

The early and precise diagnosis of dengue infection in the laboratory is of

paramount importance for disease control. It was estimated that the
number of cases of dengue misdiagnosed could reach a record of 50% of
all cases, mainly due to a wide disparity in dengue signs and symptoms
that conflict with symptoms of other viral infections, particularly for
people living in or traveling to endemic areas of tropical infectious
diseases. Until the antiviral vaccine is available, early and accurate
diagnosis relies heavily on the prevention of serious cases and the
reduction of the disease’s economic burden. To date, two screening
methods have been employed for early diagnosis of the disease. The first
is a direct approach for the acute dengue disease phase which is focused
on an antigen detection of genomic RNA from viremic patient’s blood
samples. The second is an indirect approach that relies on serological tests
to detect dengue-related immunoglobulins by Mac-ELISA for the capture
of real IgM or indirect ELISA for the capture of antiDEN IgGs.

Dengue diagnosis is usually performed clinically on the basis of recorded

symptoms and physical examination, especially in endemic areas.
However, early dengue fever can be difficult to differentiate from other
viral infections. Tourniquet testing, which is particularly useful in
environments where laboratory tests are not available, includes applying
a blood pressure cuff, inflating it to the midpoint between diastolic and
systolic pressure for 5 minutes, and then counting any petechial
hemorrhages that occur. The higher number of petechiae makes dengue
diagnosis more likely; the lower limit for diagnosis is variably specified
as 10–20 petechiae per 2.5 cm2

8. Treatment
There are no particular antiviral medicines for dengue, but it is necessary
to maintain a proper fluid balance. Treatment is dependent on the severity
of the symptoms. Those who can drink and pass urine have no warning
signs can be treated with daily follow-up and oral rehydration therapy at
home. Those who have serious health problems, who have warning signs,
or who are unable to handle daily follow-up should be admitted to the
hospital for treatment. For areas with access to an intensive care unit,
treatment should be given for those with extreme dengue fever.
Intravenous hydration usually takes 1 or 2 days, if necessary. Fluid
administration dose is titrated to 0.5–1 mL/kg per hour of urinary output,
stabilizing vital signs, and normalizing hematocrit. The volume of fluid
that is provided should be the smallest to achieve such markers. Bearing
in mind the risk of infection, invasive medical procedures such as
nasogastric intubation, intramuscular injections, and arterial punctures
should be avoided. Paracetamol (acetaminophen) is used for fever and
nausea, and it is important to avoid nonsteroidal anti-inflammatory drugs
such as ibuprofen and acetylsalicylic acid as they may increase the risk of
bleeding. For patients with compromised vital signs faced with declining
hematocrit, blood transfusion should begin early, rather than waiting for
the concentration of hemoglobin to decline to some predetermined “cause
of transfusion” level. It is advised to deliver red blood cells or whole
blood; platelets and fresh, frozen plasma are not typically recommended.
Intravenous fluids are removed during the recovery phase to avoid fluid
overload. When fluid overload occurs and vital signs are stable, stopping
the administration of fluid can be all that is required to remove excess
fluid. If the individual is outside the critical phase, a diuretic loop, such as
furosemide, may be used to remove excess fluid from circulation.

9. Prevention
In December 2015, after decades of research and clinical progress, the
first dengue vaccine (CYD-TDV or Dengvaxia®, by Sanofi Pasteur) was
authorized. Now regulatory authorities have approved it in ~20 countries.

CYD-TDV was found to be effective and safe in clinical trials in people

who had past infections with the dengue virus (seropositive individuals).
It does, however, bring an increased risk of severe dengue in those who
undergo their first normal dengue infection after vaccination (those who
were seronegative at vaccination time). It was confirmed in November
2017 by the results of an additional retrospective study analysis which
determines the serostatus at the time of vaccination.

Pre-vaccination screening is the recommended strategy for countries

which consider vaccination as part of their dengue control program. With
this approach only individuals under evidence of past dengue infection
would be vaccinated (based on an antibody test or confirmed dengue
infection in the past by a verified laboratory). Decisions on implementing
a pre-vaccination screening strategy would require careful country-level
evaluation, including consideration of the sensitivity and specificity of the
available tests and local priorities, dengue epidemiology, country-specific
hospitalization levels, and availability of both CYD-TDV and screening
tests.

But prevention depends on the monitoring and safety of the bite of the
mosquito that transmits it. The primary tool used to monitor Aedes
aegypti is by destroying its habitats, which include standing water in
urban areas (e.g., abandoned tires, ponds, irrigation ditches, and open
barrels). If habitat destruction is not possible, the application of
insecticides or biological control agents to standing water is another
option. Reducing open water collection is the preferred and simplest
method of control. Generalized spraying is often done with
organophosphate or pyrethroid insecticides but is not considered
successful. People can avoid mosquito bites by wearing clothes that
completely cover the skin, wearing a repellent scarf, or staying in air-
conditioned, screened, or nested areas. However, these approaches do not
seem to be sufficiently effective, as the frequency of outbreaks in certain
areas appears to be increasing, probably because urbanization is
increasing the habitat of Aedes mosquitoes; however, the range of diseases
appears to be expanding, possibly due to climate change.

10. Conclusion
Dengue fever is a terrible disease and a growing public health problem. A
rapid increase in unplanned urbanization leads to more mosquito breeding
sites, hence a greater number of people are exposed to Aedes
Aegypti mosquitoes bite. These include semi-urban and slum areas where
household water storage is normal and where solid waste disposal
facilities are inadequate. The urgent need for a vaccine to minimize
morbidity and mortality due to this disease has been recognized in a cost-
effective manner in recent years.