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Asian J. Res. Infect. Dis., vol. 14, no. 1, pp. 26-33, 2023
Asian Journal of Research in Infectious Diseases
Volume 14, Issue 1, Page 26-33, 2023; Article no.AJRID.100500
ISSN: 2582-3221
Dengue Fever: Etiology, Diagnosis,
Prevention and Treatment
Clement Ugochukwu Nyenke a*, Brenda Anyakwe Nnokam b,
RoseMary Kaiso Esiere c and Rhoda Nwalozie d
a Department of Medical Laboratory Science, PAMO University of Medical Sciences, Rivers State,
Nigeria.
b Department of Family Medicine, College of Medicine, Rivers State University, Port Harcourt,
Rivers State, Nigeria.
c Department of Medical Microbiology/Parasitology, University of Calabar Teaching Hospital,
Calabar, Cross River State, Nigeria.
d Department of Medical Laboratory Science, Rivers State University, Port Harcourt,
Rivers State, Nigeria.
Authors’ contributions
This work was carried out in collaboration among all authors. All authors read and approved the final
manuscript.
Article Information
DOI: 10.9734/AJRID/2023/v14i1279
Open Peer Review History:
This journal follows the Advanced Open Peer Review policy. Identity of the Reviewers, Editor(s) and additional Reviewers,
peer review comments, different versions of the manuscript, comments of the editors, etc are available here:
https://www.sdiarticle5.com/review-history/100500
Received: 03/05/2023
Accepted: 05/07/2023
Published: 15/07/2023
ABSTRACT
Dengue fever (break-bone fever) is a viral disease transmitted by Aedes mosquitoes. It is caused
by the Dengue virus, which is a single positive-stranded RNA virus belonging to the Flaviviridae
family. Dengue fever is prevalent in tropical and subtropical areas and is a significant public health
concern in many countries, including`g Nigeria. The disease is characterized by symptoms such as
high fever, headache, body aches, nausea, vomiting, swollen glands, and rash. In severe cases,
dengue fever can lead to complications such as bleeding, organ impairment, and dengue shock
syndrome. Diagnosing dengue fever can be challenging, especially in areas where it is endemic. In
endemic locations, diagnosis is often made clinically based on the patient's reported symptoms and
Review Article
Nyenke et al.; Asian J. Res. Infect. Dis., vol. 14, no. 1, pp. 26-33, 2023; Article no.AJRID.100500
27
a physical examination. Tourniquet testing, which involves applying a blood pressure cuff and
counting any petechial hemorrhages, can help in the diagnosis. Laboratory methods, including full
blood count, cell culture, nucleic acid identification (PCR), and serology, can be used to confirm the
diagnosis. Preventing dengue fever involves controlling the mosquito vector and protecting oneself
from mosquito bites. Measures such as eliminating mosquito breeding sites, using insect repellents,
wearing protective clothing, and using bed nets can help prevent mosquito bites. Vaccination
against dengue is also available, with the Dengvaxia vaccine being used in some countries. There
is no specific antiviral treatment for dengue fever. Management focuses on supportive care,
maintaining a healthy fluid balance, and relieving symptoms such as fever and pain. Severe cases
may require hospitalization and intensive medical care. In Nigeria, dengue fever is often
misdiagnosed or overlooked due to similarities with other febrile illnesses like malaria. This can lead
to underreporting and inadequate management of dengue cases. Increasing awareness among
healthcare professionals and the general population is crucial for early detection and appropriate
management of dengue fever in Nigeria. In conclusion dengue fever is a viral disease transmitted
by mosquitoes, primarily Aedes species. It is a significant global health concern, including in
Nigeria. Early diagnosis, prevention measures, and supportive care are essential in managing
dengue fever and reducing its impact on public health. This review is aimed at discussing the
current issues of Dengue fever with focus on Nigeria.
Keywords: Dengue; fever; symptoms; virus; Aedes; mosquito; laboratory.
1. INTRODUCTION
Dengue fever (break-bone fever) is a viral
disease transmitted by a species of Aedes
mosquitos [1]. It occurs more frequently in
tropical and subtropical areas [2]. According to
the WHO [2] report, majority of dengue patients
are asymptomatic. Yet, those who experience a
high temperature, headache, body aches,
nausea, and rash are the most typical symptoms.
Most people recover within 1 to 2 weeks. Some
dengue patients get severe illness and require
hospitalization.
Dengue was widespread in more than 120
countries as of 2019 [2]. According to the study
conducted by Shepard et al. [3], over 60 million
symptomatic infections were reported in 2013;
18% of these led to hospital admissions, and
13,600 people died as a result. Dengue cases
are predicted to cost $9 billion globally [3].
Twelve Southeast Asian nations were expected
to have roughly 3 million cases and 6,000 deaths
annually throughout the decade of the 2000s [4].
Amarasinghe et al. [5] reported that there have
been reports of dengue infection in at least 22
African nations, although it is likely prevalent in
all of them, with 20% of the populace at risk. This
places dengue among the most widespread
vector-borne illness around the globe [6].
The majority of infections are contracted from
urban settings [7]. With growth of villages, towns,
and cities in locations where it is frequent, as well
as greater movement of people, has increased
the number of outbreaks and circulation of
viruses in recent decades. Dengue, which was
once exclusive to Southeast Asia, has now
expanded to southern China in East Asia, Pacific
Ocean countries, and the Americas according to
Gubler [7]. Reiter [8] noted that this could be a
danger to Europe. The WHO Territories of Africa,
the Americas, the Eastern Mediterranean, South-
East Asia, and the Western Pacific are now
home to more than 100 nations where the illness
is endemic. With Asia accounting for roughly
70% of the global illness load, the Americas,
South-East Asia, and Western Pacific are the
areas most severely impacted [2]. While
serologic evidence showing Dengue infections
are widespread in various countries across
Africa, the burden of dengue is still relatively
poorly reported [9]. According to recent findings,
dengue may be a significant contributor to acute
fevers in Nigeria [10], despite the fact that many
persons who visit medical institutions
complaining of fever are administered with an
antimalarial drug without further testing. The
primary dengue mosquito vectors, Aedes aegypti
and Ae. albopictus, are well documented, and
serologic data suggests Dengue virus infections
exist in some places [9]. Unfortunately, more
thorough and generalizable surveys that would
provide data on the incidence of Dengue
infection in Nigeria are unavailable [11-13].
Malaria and dengue fever are frequently
confused in Nigeria. This might be due to the fact
that dengue and malaria both have symptoms
that are similar and that malaria is a prevalent
Nyenke et al.; Asian J. Res. Infect. Dis., vol. 14, no. 1, pp. 26-33, 2023; Article no.AJRID.100500
28
endemic disease in the area [14]. According to
the study of Chukwuma et al. [15], when the
attending clinician sees fit, many feverish
individuals in the area are occasionally
diagnosed with pyrexia of unknown origin,
typhoid fever, or malaria. Even when a test for
the malaria parasite is negative or when a patient
does not respond to anti-malarial medication, the
majority of these patients still lack a diagnosis.
According to the aforementioned, dengue
patients are frequently mistaken as malaria and
go untreated. This has the consequence of
creating anti-malaria tolerance in the general
population due to the indiscriminate use of anti-
malarial drugs [14]. This therefore necessitates
for this review on the current level of awareness
of the Nigerian populace on Dengue fever.
2. CAUSE
Dengue fever is caused Dengue virus, a single
positive-stranded RNA virus carried by
mosquitoes, belonging to the Flaviviridae family
and genus Flavivirus [16]. Yellow fever virus,
West Nile virus, Zika virus, Japanese
encephalitis virus, tick-borne encephalitis virus,
Kyasanur forest disease virus, and Omsk
hemorrhagic fever virus are additional relatives of
the same genus [17]. According to Howard-
Jones et al. [17], since the majority are spread by
arthropods (such as mosquitoes or ticks), they
are also known as arboviruses (arthropod-borne
viruses).
The DNA (genetic material) of dengue virus
consists of approximately 11,000 nucleotide
bases that code for the three different protein
types (C, prM, and E) which make up the viral
particles as well as seven other non-structural
protein molecules (NS1, NS2a, NS2b, NS3,
NS4a, NS4b, and NS5) that are only present in
host's infected cells but are necessary for virus
replication [18]. A research carried by Normile
[19] reported that there are five different
serotypes of the virus, and the first four are
known as DENV-1, DENV-2, DENV-3, and
DENV-4. In 2013, the fifth strain was revealed
[19]. The antigenicity of each serotype is used to
distinguish it from the others [20].
3. SIGNS AND SYMPTOMS
Studies conducted by Reiter [8] and Whitehorn
[21] revealed that most dengue virus infected
individuals (80%) are asymptomatic or only
experience minor symptoms like a simple fever
[8,21]. About 5% of people infected with dengue
experience severe more severe illnesses, and
only a small percentage of those are life-
threatening [21]. The incubation period (the
amount of time between exposure and the
beginning of symptoms) is typically between four
and seven days, but it can be as long as fourteen
days [7]. Hence, if symptoms appear more than
14 days after coming home from endemic
locations, dengue fever is unlikely to be present
in those individuals [22]. Common cold and
gastroenteritis-like symptoms have been
reported to frequently affect children (vomiting
and diarrhea) [23], are more likely to experience
serious difficulties noted Simmons et al. [24],
although the first few symptoms are typically
minor and include a high fever.
Clinical manifestation of dengue includes; high
fever (40°C/104°F), excruciating headache, eye
pain, aches in the muscles and joints, nausea,
vomiting, swollen glands, and rash are some of
the symptoms. Chronic dengue is more likely to
affect people who have already been infected
once [2]. Based on WHO [2] report, intense
stomach pain, continuous vomiting, quick
breathing, bleeding gums or nose, exhaustion,
restlessness, blood in vomit or stool, extreme
thirst, pale and chilly skin, and a weak sensation
are all severe dengue symptoms that may
appear after the fever has subsided. It is
important for people to seek professional medical
attention right away if they experience these
serious symptoms. After recovering, dengue
patients may experience fatigue for several
weeks.
4. TRANSMISSION
Aedes mosquitoes, especially, A. aegypti, are the
main carriers of the dengue virus [1-2]. Typically,
these mosquitoes inhabit the area between 35°
North and 35° South, below an elevation of 1000
meters (3,300 ft) [2]. Although they mainly bite in
the morning and the evening, they can bite and
spread infection at any time of the day [2]. Aedes
albopictus, Aedes polynesiensis, and Aedes
scutellaris are other Aedes species capable of
spreading the disease. The virus's main host are
humans [17], although none human primates can
play host to the virus also [25]. According to the
CDC [26], one bite is enough to spread an
infection.
Exposure to contaminated blood, organs, or
other tissues can result in bloodborne
transmission due to the about 7-day viremia in
humans (such as bone marrow) [26]. Moreover,
Nyenke et al.; Asian J. Res. Infect. Dis., vol. 14, no. 1, pp. 26-33, 2023; Article no.AJRID.100500
29
perinatal dengue transmission happens when the
woman contracts the disease right before giving
birth. In this case, infection happens through
microtransfusions after the placenta separates or
through mucosal contact with the maternal blood
after delivery. No evidence of congenital
transmission has been found. Breast milk may
also be a source of dengue virus transmission.
There is no proof that it can be passed via sexual
intercourse [26].
5. DIAGNOSIS
5.1 Physical Examination
In endemic locations, in particular, the screening
of dengue is often made clinically, based on the
patient's reported symptoms and a physical
examination [21]. Early sickness, however, might
be challenging to distinguish from other viral
infections [22]. Fever with alongside nausea and
vomiting and any of the symptoms, such as,
rash, widespread aches, a low white blood cell
count, a positive tourniquet test, or any warning
sign in a resident of an endemic area, constitutes
a probable diagnosis [27].
5.2 Tourniquet Screening
The tourniquet testing, which involves applying a
blood pressure cuff at a pressure between the
diastolic and systolic for five minutes, followed by
counting any petechial hemorrhages; a higher
number increases the likelihood that the patient
has dengue, with a cut off of more than 10 to 20
per 1 inch2 being used as a guide (6.25 cm2)
[27].
Simmons [24] reported that, everyone with a
fever within two weeks of being in the tropics or
subtropics should be diagnosed, according to
the condition's official diagnosis. It can be
challenging to differentiate between dengue fever
and chikungunya, a closely related viral virus that
has a number of identical symptoms as dengue
and occurs in comparable geographic locations
[28]. Testing are frequently carried out to rule out
other disorders that have the same symptoms,
such as influenza, measles, leptospirosis, viral
hemorrhagic fever, typhoid fever, and
meningococcal disease [22,27]. Dengue and zika
fever symptoms are identical [29].
5.3 Full Blood Count Testing
Ranjit [22] noted that, decreased white blood cell
count is the initial change that can be identified
through laboratory testing; this is followed
possibly by a low platelet count and metabolic
acidosis. Reduced platelets and white blood cells
are frequently correlated with somewhat high
levels of the liver's aminotransferases (AST
and ALT). [24]. When a disease is chronic,
plasma leakage causes hypoalbuminemia and
hemoconcentration, as shown by an increasing
hematocrit [22]. Physical examination can reveal
pleural effusions or ascites when they are
substantial [22], however, the presence of fluid
on ultrasound can be helpful with the earlier
diagnosis of dengue shock syndrome [21]. The
inaccessibility of ultrasonography in many
circumstances limits its utilization. A study by
Simmons [24] showed that if the peripheral
vascular collapse occurs and the pulse pressure
falls to or below 20 mm Hg, dengue shock
syndrome is present. Children's peripheral
vascular collapse can be identified by slow
capillary refill, a fast heartbeat, or chilled
extremities [27]. Whereas early diagnosis of
potentially dangerous diseases is aided by
warning signs, the proof for any given clinical or
laboratory indicator is poor [6].
5.4 Cell Culture, Nucleic Acid
Identification, Polymerase Chain
Reaction (PCR) and Serology
Microbiological laboratory screening can be
employed in the confirmation diagnosis of
dengue fever [27,30]. This is often accomplished
through isolation of virus in cell cultures, nucleic
acid identification using PCR, viral antigen
detection (such as using NS1), or particular
antibodies (serology) [27]. However, WHO [27]
noted that whereas virus isolation and nucleic
acid detection are more precise than antigen
detection, these techniques are less frequently
used because of their higher costs. The
sensitivity of NS1 identification during the febrile
stage of an initial infection may be higher than
90%, but only 60-80% in secondary infection
[24]. In the initial phases of the illness, all testing
might come back negative [18]. In other to obtain
accurate results, Polymerase Chain Reaction
and viral antigen detection techniques can be
employed [24]. A PCR test that can be
conducted on equipment used to diagnose
influenza was launched in 2012; this is probably
going to make PCR-based diagnosis more
accessible [31].
With the exception of serology, these laboratory
tests are only useful for diagnosis in the acute
stage of the illness. In the later stages of the
Nyenke et al.; Asian J. Res. Infect. Dis., vol. 14, no. 1, pp. 26-33, 2023; Article no.AJRID.100500
30
infection, tests for IgG and IgM antibodies
specific to the dengue virus can be helpful in
confirming a diagnosis. After 5-7 days, both IgG
and IgM are created. IgM is created after
reinfection but is identified at its maximum levels
(titers) after an initial infection. IgM disappears 30
to 90 days after an initial infection, but sooner
after subsequent infections. IgG, in contrast, can
still be detected after more than 60 years and, in
the absence of symptoms, serves as a reliable
sign of previous infection. IgG levels in the blood
spike 14 to 21 days after an initial infection.
Levels peak early and titers are typically higher in
future re-infections. IgG and IgM both offer
defense against the viral serotype that is
invading cells [7,18,28]. Simmons [24] reported
that with recent infections or immunizations with
the yellow fever virus or Japanese encephalitis,
there may be cross-reactivity with other
flaviviruses in tests for IgG and IgM antibodies,
which could lead to a false positive. Until blood
samples are taken 14 days apart and a higher
than fourfold increase in levels of particular IgG
is identified, the detection of IgG alone is not
deemed diagnostic. The presence of IgM is
regarded as diagnostic in a patient with
symptoms [7].
6. PREVENTION
According to the WHO [27], control of the vector
(mosquito) that spreads the disease and
protection from its bites are essential for
prevention. The World Health Organization
(WHO) suggests a five-part integrated vector
control approach which includes; ensuring that
public health organizations and communities are
strengthened through advocacy, social
mobilization, and legislation; collaboration
between the public and private sectors in the
health sector; a coordinated strategy for disease
prevention that makes the best use of available
resources; and building capacity and using
evidence-based decision-making to ensure that
any interventions are targeted effectively and
appropriately [27].
Eradicating the habitats of A. aegypti is the main
strategy of management [27]. This is
accomplished either by eliminating open water
sources or, if that is not practicable, by spraying
insecticides or biological control agents on the
affected areas. Although it is occasionally done,
generalized spraying with organophosphate or
pyrethroid insecticides is not believed to be
successful [8]. Given the potential harm that
pesticides may cause to human health and the
greater logistical challenges presented by control
agents, reducing open water collections by
environmental change is the preferred way of
management [27]. Wearing clothes that
completely covers the skin, sleeping with
mosquito netting, and/or applying insect repellent
are all ways that people can avoid getting bitten
by mosquitoes (DEET being the most effective)
[26]. Normile [19] reported that the incidence of
outbreaks appears to be increasing in some
places, most likely as a result of urbanization
expanding the habitat of A. aegypti. While these
steps can be successful at lowering an
individual's risk of exposure, they do little to
mitigate this trend. Additionally, it seems like the
disease is spreading farther, perhaps as a result
of climate change [19].
Susie [32] reported that dengue fever vaccine
with mixed results went on sale in the Philippines
and Indonesia in 2016. Mexico, Brazil, El
Salvador, Costa Rica, Singapore, Paraguay,
most of Europe, and the United States have all
given their approval for its use [33]. Only those
with a prior dengue illness or groups where the
majority (>80%) of people have been exposed
before age 9 are advised to get the vaccination
[34]. There is indication that it may exacerbate
subsequent infections in people who have never
had one [33]. Due to this, even in locations
where the disease is prevalent, Prescribe does
not deem it appropriate for widespread
immunization [35].
The WHO [2] recommends rest, drinking of lots
of fluids, use of acetaminophen (paracetamol) for
discomfort, avoidance of non-steroidal anti-
inflammatory medicines like ibuprofen and
aspirin, watching for severe symptoms, and
getting in touch with your doctor right
immediately as a way to manage dengue
infection. Dengvaxia vaccine has so far received
approval and licensing in several nations.
Nevertheless, this vaccination can only provide
protection to people who have a history of
dengue infection. There are other dengue
vaccine candidates being investigated [2].
According Guy et al. [36], Dengvaxia vaccine is
centered on a weakened mixture of the four
serotypes of dengue and the yellow fever
virus. The vaccination was 66% successful in
studies conducting by Torres [34], preventing
more than 80 to 90% of chronic cases. For
some people, this is less than ideal noted Pollack
[37].
Nyenke et al.; Asian J. Res. Infect. Dis., vol. 14, no. 1, pp. 26-33, 2023; Article no.AJRID.100500
31
7. TREATMENT
Although there are no specific antiviral
medications for dengue, maintaining a healthy
fluid balance is crucial according to Simmons
[24]. Symptoms determine the course of
treatment [27]. With regular monitoring and oral
rehydration therapy, patients who are able to
drink, are passing urine, have no "warning
signals," and are generally healthy can be
treated at home. People who require hospital
treatment include those who have additional
health issues, exhibit "warning signs," or are
incapable of managing routine follow-up [22].
Patients who have chronic dengue cases should
receive care in a location with access to an
Intensive Care Unit (ICU) [27].
Usually, intravenous hydration is only necessary
for one or two days, if at all it is needed [27].
A quick dose of 20 mL/kg is appropriate for
children with dengue shock [38]. Following the
stabilization of vital signs, normalization of the
hematocrit, and a urinary output of 0.5–1
mL/kg/h, the rate of fluid delivery is adjusted [22].
It is advised to use the least amount of fluid
necessary to accomplish this [27].
8. CONCLUSION
Dengue fever remains one of the endemic
diseases in sub-Saharan Africa, particularly, in
Nigeria. It is even of great threat seeing that it
shares similar symptoms with malaria and other
mosquito borne disease and as a result calls for
greater awareness and measures towards it
minimum control in the Nigerian nation.
Professionals should also be trained and
equipped to detect dengue especially when
diagnosis do not reflect malaria and sickness
persists in a patient.
COMPETING INTERESTS
Authors have declared that no competing
interests exist.
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© 2023 Nyenke et al.; This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.
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