CHAPTER 9

Dengue Fever

1. Define the meaning of Dengue fever

2. Discuss the Signs & Symptoms of Dengue fever.
3. Discuss the prevention of the Dengue fever.

Introduction:

Dengue fever

is a mosquito-borne tropical disease caused by the dengue virus. Symptoms

typically begin three to fourteen days after infection. These may include a
high fever, headache, vomiting, muscle and joint pains, and a characteristic skin
rash. Recovery generally takes two to seven days. In a small proportion of cases,
the disease develops into severe dengue, also known as dengue hemorrhagic
fever, resulting in bleeding, low levels of blood platelets and blood
plasma leakage, or into dengue shock syndrome, where dangerously low blood
pressure occurs
Dengue is spread by several species of female mosquitoes of the Aedes type,
principally A. aegypti. The virus has five types; infection with one type usually
gives lifelong immunity to that type, but only short-term immunity to the
others Subsequent infection with a different type increases the risk of severe
complications. A number of tests are available to confirm the diagnosis including
detecting antibodies to the virus or it’s RNA.
A vaccine for dengue fever has been approved and is commercially available in a
number of countries. As of 2018, the vaccine is only recommended in individuals
who have been previously infected or, in populations with a high rate of prior
infection by age nine. Other methods of prevention include reducing mosquito
habitat and limiting exposure to bites This may be done by getting rid of or
covering standing water and wearing clothing that covers much of the
body Treatment of acute dengue is supportive and includes giving fluid either by
mouth or intravenously for mild or moderate disease For more severe
cases, blood transfusion may be required. About half a million people require
hospital admission every year.] Paracetamol (acetaminophen) is recommended
instead of no steroidal anti-inflammatory drugs (NSAIDs) for fever
reduction and pain relief in dengue due to an increased risk of bleeding from
NSAID use. Dengue has become a global problem since the Second World
War and is common in more than 120 countries, mainly in Asia and South
America.[5][13][14] About 390 million people are infected a year and approximately
40,000 die In 2019 a significant increase in the number of cases was seen. The
earliest descriptions of an outbreak date from 1779 its viral cause and spread
were understood by the early 20th century. Apart from eliminating the
mosquitos, work is ongoing for medication targeted directly at the virus it is
classified as a neglected tropical disease

Signs and Symptoms

Typically, people infected with dengue virus are asymptomatic (80%) or have only
mild symptoms such as an uncomplicated fever. Others have more severe illness
(5%), and in a small proportion it is life-threatening. The incubation period (time
between exposure and onset of symptoms) ranges from 3 to 14 days, but most
often it is 4 to 7 days Therefore, travelers returning from endemic areas are
unlikely to have dengue fever if symptoms start more than 14 days after arriving
home Children often experience symptoms similar to those of the common
cold and gastroenteritis (vomiting and diarrhea)[24] and have a greater risk of
severe complications though initial symptoms are generally mild but include
high fever

Signs & Symptoms

1] Fever longer than 3 days

2] Rashes within3-4 days after the start of fever
3] Headache
4] Muscle and joint pains
5] Vomiting
6] Loss of appetite
7] Abdominal pain
Clinical course

The characteristic symptoms of dengue are sudden-onset fever, headache

(typically located behind the eyes), muscle and joint pains, and a rash. An
alternative name for dengue, "break bone fever", comes from the associated
muscle and joint pains. The course of infection is divided into three phases:
febrile, critical, and recover

The febrile phase involves high fever, potentially over 40 °C (104 °F), and is
associated with generalized pain and a headache; this usually lasts two to seven
days. Nausea and vomiting may also occur A rash occurs in 50–80% of those
with symptoms in the first or second day of symptoms as flushed skin, or later
in the course of illness (days 4–7), as a measles-like rash. A rash described as
"islands of white in a sea of red" has also been observed.] Some petechial (small
red spots that do not disappear when the skin is pressed, which are caused by
broken capillaries) can appear at this point as may some mild bleeding from
the mucous membranes of the mouth and nose The fever itself is
classically biphasic or saddleback in nature, breaking and then returning for one
or two days

Cause

Virology
Dengue fever virus (DENV) is an RNA virus of the family Flaviviridae;
genus Flavivirus. Other members of the same genus include yellow fever
virus, West Nile virus, Zika virus, St. Louis encephalitis virus, Japanese
encephalitis virus, tick-borne encephalitis virus, Kyasanur forest disease virus,
and Omsk hemorrhagic fever virus Most are transmitted
by arthropods (mosquitos or ticks), and are therefore also referred to
as parvoviruses (arthropod-borne viruses
The dengue virus genome (genetic material) contains about 11,000 nucleotide
bases, which code for the three different types of protein molecules (C, prM and
E) that form the virus particle and seven other non-structural protein molecules
(NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5) that are found in infected host cells
only and are required for replication of the virus.
 There are five strains of the virus, called serotypes, of which the first four are
referred to as DENV-1, DENV-2, DENV-3 and DENV-4. The fifth type was
announced in 2013. The distinctions between the serotypes are based on
their antigenicity.

Transmission

Dengue virus is primarily transmitted by Aides mosquitos, particularly A.

aegypti. These mosquitos usually live between the latitudes of 35° north and
35° South below an elevation of 1,000 meters (3,300 ft). They typically bite during
the early morning and in the evening,[35][36] but they may bite and thus spread
infection at any time of day Other Aedes species that transmit the disease
include A. albopictus, A. polynesiensis and A. scutellaris. Humans are the
primary host of the virus, but it also circulates in nonhuman primates. An
infection can be acquired via a single bite a female mosquito that takes a blood
meal from a person infected with dengue fever, during the initial 2- to 10-day
febrile period, becomes itself infected with the virus in the cells lining its
gut. About 8–10 days later, the virus spreads to other tissues including the
mosquito's salivary glands and is subsequently released into its saliva. The virus
seems to have no detrimental effect on the mosquito, which remains infected for
life. Aedes aegypti is particularly involved, as it prefers
Predisposition
to lay its eggs in artificial water containers, to live in
close proximity to humans, and to feed on people rather
than other vertebrates Dengue can also be transmitted via infected
Severe disease is more common in babies and young children, and in contrast
to many other infections, it is more common in children who are relatively well
nourished Other risk factors for severe disease include female sex, high body
mass index,] and viral load.] While each serotype can cause the full spectrum of
disease virus strain is a risk factor Infection with one serotype is thought to
produce lifelong immunity to that type, but only short-term protection against
the other three. The risk of severe disease from secondary infection increases if
someone previously exposed to serotype DENV-1 contracts serotype DENV-2 or
DENV-3, or if someone previously exposed to DENV-3
Mechanism acquires DENV-2.
When a mosquito carrying dengue virus bites a person, the virus
enters the skin together with the mosquito's saliva. It binds to and enters white blood
cells, and reproduces inside the cells while they move throughout the body. The
white blood cells respond by producing several signaling proteins, such
as cytokines and interferon’s, which are responsible for many of the symptoms,
such as the fever, the flu-like symptoms, and the severe pains. In severe
infection, the virus production inside the body is greatly increased, and many
more organs (such as the liver and the bone marrow) can be affected.
Viral Replication

Once inside the skin, dengue virus binds to Langerhans cells (a population
of dendritic cells in the skin that identifies pathogens).] The virus enters the
cells through binding between viral proteins and membrane proteins on the
Langerhans cell, specifically, the C-type lections called DC-SIGN, mannose
receptor and CLEC5A. DC-SIGN, a non-specific receptor for foreign material on
dendritic cells, seems to be the main point of entry. The dendritic cell moves to
the nearest lymph node. Meanwhile, the virus genome is translated in
membrane-bound vesicles on the cell's endoplasmic reticulum, where the cell's
protein synthesis apparatus produces new viral proteins that replicate the viral
RNA and begin to form viral particles. Immature virus particles are transported
to the Golgi apparatus, the part of the cell where some of the proteins receive
necessary sugar chains (glycoproteins). The now mature new viruses are released
by exocytosis. They are then able to enter other white blood cells, such
as monocytes and macrophages.
for phagocytosis (ingestion by specialized cells and destruction), but some bind
the virus less well and appear instead to deliver the virus into a part of the
phagocytes where it is not destroyed but can replicate further
Severe Disease

It is not entirely clear why secondary infection with a different strain of dengue
virus places people at risk of dengue hemorrhagic fever and dengue shock
syndrome. The most widely accepted hypothesis is that of antibody-dependent
enhancement (ADE). The exact mechanism behind ADE is unclear. It may be
caused by poor binding of non-neutralizing antibodies and delivery into the
wrong compartment of white blood cells that have ingested the virus for
destruction. There is a suspicion that ADE is not the only mechanism underlying
severe dengue-related complications, and various lines of research have implied
a role for T cells and soluble factors such as cytokines and the complement
system. Severe disease is marked by the problems of capillary permeability (an
allowance of fluid and protein normally contained within the blood to pass) and
disordered blood clotting. These changes appear associated with a disordered
state of the endothelial glycocalyx, which acts as a molecular filter of blood
components
Diagnosis

The diagnosis of dengue is typically made clinically, on the basis of reported

symptoms and physical examination; this applies especially in endemic
areas However, early disease can be difficult to differentiate from other viral
infections.] A probable diagnosis is based on the findings of fever plus two of the
following: nausea and vomiting, rash, generalized pains, low white blood cell
count, positive tourniquet test, or any warning sign (see table) in someone who
lives in an endemic area Warning signs typically occur before the onset of severe
dengue.] The tourniquet test, which is particularly useful in settings where no
laboratory investigations are readily available, involves the application of a blood
pressure cuff at between the diastolic and systolic pressure for five minutes,
followed by the counting of any petechial hemorrhages; a higher number makes
a diagnosis of dengue more likely with the cut off being more than 10 to 20 per
1 inch2 (6.25 cm2
The diagnosis should be considered in anyone who develops a fever within two
weeks of being in the tropics or subtropics.[25] It can be difficult to distinguish
dengue fever and chikungunya, a similar viral infection that shares many
symptoms and occurs in similar parts of the world to dengue. Often,
investigations are performed to exclude other conditions that cause similar
symptoms, such as malaria, leptospirosis, viral hemorrhagic fever, typhoid
fever, meningococcal disease, measles, and influenza. Zika fever also has similar
symptoms as dengue

Prevention:

Prevention depends on control of and protection from the bites of the mosquito
that transmits it. The World Health Organization recommends an Integrated
Vector Control program consisting of five elements: Advocacy, social mobilization
and legislation to ensure that public health bodies and communities are
strengthened;

1. Collaboration between the health and other sectors (public and private);
2. An integrated approach to disease control to maximize the use of
resources;
3. Evidence-based decision making to ensure any interventions are targeted
appropriately; and
4. Capacity-building to ensure an adequate response to the local situation.
The primary method of controlling A. aegypti is by eliminating its habitats.] This
is done by getting rid of open sources of water, or if this is not possible, by
adding insecticides or biological control agents to these areas. Generalized
spraying with organophosphate or parathyroid insecticides, while sometimes
done, is not thought to be effective Reducing open collections of water through
environmental modification is the preferred method of control, given the
concerns of negative health effects from insecticides and greater logistical
difficulties with control agents.

Vaccine In 2016 a partially effective vaccine for dengue

fever became commercially available in the Philippines
and Indonesia. It has been approved for use by Mexico,
Brazil, El Salvador, Costa Rica, Singapore, Paraguay, much of Europe, and the
United States The vaccine is only recommended in individuals who have had a
prior dengue infection or in populations where most (>80%) of people have been
infected by age 9 In those who have not had a prior infection there is evidence it
may worsen subsequent infections The vaccine is produced by Sanofi and goes
by the brand name Dengvaxia. It is based on a weakened combination of
the yellow fever virus and each of the four dengue serotypes. Studies of the
vaccine found it was 66% effective and prevented more than 80 to 90% of severe
cases this is less than wished for by some. In Indonesia it costs about US$207
for the recommended three doses

Anti-dengue day
International Anti-Dengue Day is observed every year
on 15 June The idea was first agreed upon in 2010 with the first event held
in Jakarta, Indonesia in 2011 Further events were held in 2012
in Yangon, Myanmar and in 2013 in Vietnam Goals are to increase public
awareness about dengue, mobilize resources for its prevention and control and,
to demonstrate the Asian region's commitment in tackling the disease

Management
Are no specific antiviral drugs for dengue; however,
maintaining proper fluid balance is
important. Treatment depends on the symptoms Those who can drink, are
passing urine, have no "warning signs" and are otherwise healthy can be
managed at home with daily follow-up and oral rehydration therapy. Those who
have other health problems, have "warning signs", or cannot manage regular
follow-up should be cared for in hospital. In those with severe dengue care
should be provided in an area where there is access to an intensive care unit.[12]
Intravenous hydration, if required, is typically only needed for one or two
days.] In children with shock due to dengue a rapid dose of 20 mL/kg is
reasonable.] The rate of fluid administration is then titrated to a urinary output of
0.5–1 mL/kg/h, stable vital signs and normalization of hematocrit. The smallest
amount of fluid required to achieve this is recommended
Prognosis
Most people with dengue recover without any ongoing problems.] The risk of
death among those with severe dengue is 0.8% to 2.5%, and with adequate
treatment this is less than 1%. However, those who develop significantly low
blood pressure may have a fatality rate of up to 26%. The risk of death among
children less than five years old is four times greater than among those over the
age of 10. Elderly people are also at higher risk of a poor outcome

Epidemiology
Dengue is common in more than 120 countries. In 2013 it caused about 60
million symptomatic infections worldwide, with 18% admitted to hospital and
about 13,600 deaths.] The worldwide cost of dengue case is estimated US$9
billion For the decade of the 2000s, 12 countries in Southeast Asia were
estimated to have about 3 million infections and 6,000 deaths annually In 2019
the Philippines declared a national dengue epidemic due to the deaths reaching
622 people that year It is reported in at least 22 countries in Africa; but is likely
present in all of them with 20% of the population at risk This makes it one of the
most common vector-borne diseases worldwide
 CHAPTER WEB VIDEO
LINK

1. https://youtu.be/8LM5O-PqD_g
2. https://youtu.be/f_e1JrdYUUo
3. https://youtu.be/HAkYOOhbwos
4. https://youtu.be/SV9IrGtByNY
5. https://youtu.be/4JmBMutHRyo
6. https://youtu.be/tJhBcaT-hAc
7. https://youtu.be/x-sulfl0_e4
8. https://youtu.be/Damg7d8STcs

Sonia Gasilla-De La Cruz , National Service Training

Program ( CWTS & ROTC )
https://en.wikipedia.org/wiki/Dengue_fever