Journal of Infection and Public Health 13 (2020) 193–198

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Journal of Infection and Public Health

journal homepage: http://www.elsevier.com/locate/jiph

Diagnosis of severe dengue: Challenges, needs and opportunities

Pooi-Fong Wong a,∗ , Li-Ping Wong b,∗ , Sazaly AbuBakar c,d,e
a
Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
b
Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
c
Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
d
Tropical Infectious Diseases Research and Educational Centre (TIDREC), University of Malaya, 50603 Kuala Lumpur, Malaysia
e
WHO Collaborating Centre for Arbovirus Reference and Research (Dengue and Severe Dengue), MAA-12, University of Malaya, Kuala Lumpur, Malaysia

a r t i c l e i n f o a b s t r a c t

Article history: Background: Delayed diagnosis of dengue cases with increased risk for severe disease could lead to poor
Received 21 January 2019 disease outcome. To date there is no specific laboratory diagnostic test for severe dengue. This qualitative
Received in revised form 11 March 2019 study explored expert views regarding current issues in diagnosing severe dengue, rationale for severe
Accepted 22 July 2019
dengue-specific diagnostics, future prospects and features of potential diagnostics for severe dengue.
Methods: In-depth individual interviews with thematic saturation were conducted between May and July
Keywords:
2018. The data was analyzed using thematic analysis.
Severe dengue
Results: Based on expert opinion, diagnosis of severe dengue is challenging as it depends on astute clin-
DENV
Diagnostics
ical interpretation of non-dengue-specific clinical and laboratory findings. A specific test that detects
Challenges impending manifestation of severe dengue could 1) overcome failure in identifying severe disease for
referral or admission, 2) facilitate timely and appropriate management of plasma leakage and bleeding,
3) overcome the lack of clinical expertise and laboratory diagnosis in rural health settings. The most
important feature of any diagnostics for severe dengue is the point-of-care (POC) format where it can be
performed at or near the bedside.
Conclusion: The development of diagnostics to detect impending severe dengue is warranted to reduce
the morbidity and mortality rates of dengue infection and it should be prioritized.
© 2019 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University
for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction infections. With timely intervention, severe dengue mortality rates

Dengue is a mosquito-borne viral disease endemic in tropical
and subtropical regions around the world. Dengue virus (DENV)
is responsible for causing dengue fever (DF), which is an acute
febrile illness that is often self-limiting. A small percentage of those
who contracted the infection however, developed the severe forms
of the infection which could result in severe intravascular leak-
ages, multiple organ failures and deaths [1]. Approximately 3.9
billion people living in 128 countries are at risk of contracting
dengue [2]. An estimated 50–100 million cases of apparent infec-
tions occurred worldwide annually [3], which resulted in 22,000
deaths [4]. Because of this, DF and its more severe forms are impor-
tant public health problems globally. Early diagnosis and prompt
treatment are vital for successful management of severe DENV
∗ Corresponding authors.
E-mail addresses: pfwong@ummc.edu.my (P.-F. Wong), wonglp@um.edu.my,
wonglp@ummc.edu.my (L.-P. Wong).
can be reduced from greater than 20% to less than 1% [5].
It is well known that diagnosis of DF during routine clinical care
is challenging because the clinical and laboratory characteristics of
dengue during the febrile phase as well as during the critical phase
may overlap with other diseases prevalent in the same endemic
region. Cross-reactivity in flavivirus serology further compounded
the diagnosis of dengue [6]. Laboratory confirmation of DF can be
made from a single acute-phase serum specimen obtained early
(less than five days after fever onset) by detecting the viral genomic
sequences with RT-PCR or the presence of DENV non-structural
protein 1 (NS1) antigen by immunoassay. It is suggested that high
NS1 levels detected within the first 72 h of fever is a strong pre-
dictor of progression to the more severe disease [7]. However, the
kinetics of NS1 detection over the course of the disease in sec-
ondary infections is shorter than that of primary infections due to
the rapid anamnestic rise in NS1 cross-reacting antibodies during
the acute phase of disease, which sequesters NS1 in immune com-
plexes and renders them undetectable by immuno-capture assays
[8]. IgM against DENV can be detected as early as 3–5 days in pri-

https://doi.org/10.1016/j.jiph.2019.07.012
1876-0341/© 2019 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
194 P.-F. Wong et al. / Journal of Infection and Public Health 13 (2020) 193–198

mary infection with capture ELISA, whereas IgG in general, does administrators. The overarching goal was to highlight the critical
not appear during the acute phase of primary infection until much need for the development of laboratory diagnosis for severe dengue
later. However, during secondary DENV infection, IgG can appear and to help strengthen future research initiatives.
as early as 3 days and rises dramatically in the following two weeks
after the onset of illness due to a rapid anamnestic IgG response to
Materials and method
shared epitopes on multiple viral proteins of the first and second
infecting DENV serotypes. Hence, the ratio of IgM and IgG is a useful
We undertook a qualitative study employing insights from
differentiating indicator of primary and secondary infection [9,10]
educators, researchers, physicians, and laboratory administrators.
but is not predictive of potential severe manifestations of dengue.
In-depth, one-on-one interviews were conducted with each expert.
Currently, there is no effective antiviral therapeutics to treat
Experts were recruited through purposeful sampling techniques.
dengue, nor an effective vaccine to prevent infection. Although
Data collection continued until no new themes emerged from the
the world’s first dengue vaccine, Dengvaxia has been approved
data. Study Information Sheets detailing the background, method-
in 19 countries, recent controversy has tainted the credibility
ology, and confidentiality aspects of the study were provided to
of this dengue vaccine [11]. As a result, serological testing for
the experts prior commencing the interviews. Written informed
dengue remains as an important approach for prompt diagnosis
consent was obtained from all of the experts at the time of the
followed by appropriate treatment. In general most DF patients
interview. Interviews were conducted in English and were audio
will enter the recovery phase without progressing through the
recorded and transcribed verbatim. Ethical approval was granted by
critical phase, while others during the defervescence phase will
the Medical Ethics Committee, University Malaya Medical Centre,
progress to the more life-threatening severe dengue haemorrhagic
Kuala Lumpur, Malaysia (MEC Ref. No. 2018312-6123). Participa-
fever and shock syndrome. Because of this uncertainty, early detec-
tion was voluntary, and the interviewees were free to stop the
tion of the impending manifestation of severe forms of dengue
interview at any time. Before the interviews began, the purpose
and proper case management is important. Warning signs of the
of the study was explained again and informed verbal consent for
progression to severe dengue which may include persistent vomit-
participation in the study was obtained.
ing, severe abdominal pain, mucosal bleeding, difficulty breathing,
Interviews were conducted with the aid of an interviewer guide
signs of hypovolemic shock, and rapid decline in platelet count with
that included probes for further questioning. The content of the
an increase in haematocrit (haemoconcentration) occur in the late
interviewer guide was validated and tested in a pilot study. The
febrile phase around the time of effervescence. Clinical diagnosis
interview was semi-structured and focused on exploring the pro-
of impending severe dengue however, is a challenge persistently
cess and current challenges in diagnosis of severe dengue. The
faced by health practitioners caring after dengue patients. Upon
opening questions were: “Could you illustrate the current process
diagnosis with dengue, laboratory results and evaluation of the
involved in making diagnosis of severe dengue?” and “What are the
warning signs of progression to severe dengue are used as signs
challenges along the process of diagnosis of severe dengue?”
suggestive of likely progression to severe dengue. Severe dengue
We then queried experts on their perspectives regarding future
is commonly characterized by increased vascular permeability,
prospects and opportunities in developing diagnostics for severe
hemoconcentration (a rise in hematocrit ≥20% or signs of plasma
dengue. They were queried on the possibility of research on inven-
leakage such as pleural effusion, ascites, proteinemia), haemor-
tion or innovation of diagnostics to detect severe dengue in the
rhagic manifestations, and thrombocytopenia (low platelet count
future. We further assess perspective about the rationale for the
– 100,000/mm3 or less) [12]. However, most of these severe dis-
need of a test to diagnose potential manifestations of severe
ease manifestations are not well defined in the available guidelines
dengue. In order to assess the rationale for developing a test to
and others are based on arbitrary laboratory cut-off values. Indeed,
detect severe dengue and the extent such a test would benefit
severity is based mostly on clinical judgement and varies in differ-
the diagnostic process, the experts responded to questions such
ent clinical practice settings. Accurate, efficient, and rapid diagnosis
as: “Why is there an urgent need for a test kit to diagnose severe
of impending severe dengue is critical for prompt rigorous clini-
dengue?” Open-ended follow-up questions and probes were used
cal monitoring and care to avoid complications that could lead to
to gain further insight into the extent to which the possible diag-
mortality. In contrast, inaccurate diagnosis may cause unnecessary
nostics for severe dengue would benefit the process of diagnosis
hospital admission and in turn increases the burden to the health
and the health care setting if available. The last section of the inter-
care systems [13] especially in epidemic outbreak setting when the
view focused on gathering opinions of the desired characteristics
number of hospital beds become severely limited.
and features of a diagnostic test to detect severe dengue.
Dengue is hyperendemic in Malaysia, a tropical country located
The data was analyzed using thematic analysis (NVivo soft-
in Southeast Asia with a population of approximately 32 mil-
ware, version 11) to identify all important themes mentioned by
lion people. Malaysia also has among the highest rates of DENV
the experts. Data were assigned codes inductively and a constant
infection reported worldwide [14]. The challenges faced by local
comparative approach was taken to ensure codes were used con-
healthcare providers in making diagnosis of severe dengue have
sistently. Codes were subsequently categorized into themes. Two
never been empirically documented. There is a need to prop-
researchers worked together to identify the final themes, which
erly document these challenges to identify potential solutions
were tested against the coded transcripts to ensure they were rep-
and address the constraints in diagnosing severe dengue. To date,
resentative of the data.
there is little or no published research that provides empirical evi-
dence on issues surrounding dengue diagnostic in dengue endemic
countries. Each country has its own unique epidemiological and Results
organizational contextual challenges that warrant proper docu-
mentation. To address this, we conducted a qualitative study that Between May and July 2018, a total of five in-depth individ-
sought expert views regarding the 1) current issues faced in the ual interviews were conducted with two educators, a researcher,
diagnosis of severe dengue, 2) future prospects and opportunities a physician, and a laboratory administrator around Klang Valley,
in the development of diagnostics for severe dengue, 3) rationale Malaysia, a major location where dengue cases were concentrated
for why a test is needed, and 4) features of potential diagnostics for over the last four decades. The inclusion criteria included having a
severe dengue. In this study, we held in-depth interviews with a good understanding of current dengue and severe dengue diagnosis
diverse sample of educators, researchers, physicians and laboratory in a healthcare setting or having experience with dengue diagnosis.
 P.-F. Wong et al. / Journal of Infection and Public Health 13 (2020) 193–198
Current challenges in the diagnosis of severe dengue
Almost all of the experts noted that the current diagnosis of
severe dengue is a great challenge in clinical settings. They noted
that early diagnosis of dengue was performed by the detection
of dengue virus NS1 antigen and immunoglobulin M (IgM)/IgG
antibodies. Upon confirmation of dengue, patients were either
sent home or remained in the hospital for further observation,
depending on the physician’s judgement of the patients’ clinical
presentations and available haematological parameters.
“Usually when the patient comes in with suspected dengue,
we take blood and proceed to test whether the individual is
confirmed to have dengue. If they don’t have severe dengue,
normally patients were asked to go home and informed to mon-
itor the warning signs themselves. We don’t have enough beds
in the hospital, especially during peak dengue seasons”
“What happens right now, there is no way of telling whether
this patient or which patient will develop severe dengue, so to
be on the safe side, the doctors would usually keep patients in
hospital first, based on platelet count”
“. . .and it is not just one measurement, you have to do [a
measurement] every few hours or every day, especially the
haematocrit level. . . that is the indication that clinicians use to
determine whether the condition is getting worse.”
All experts shared the opinion that many other illnesses in trop-
ical countries with similar symptoms as dengue amplify the need
for a specific diagnostic for severe dengue.
“In Malaysia, and in many Southeast Asian countries, we have
a number of infections where early symptoms mimic infection
of dengue such as Leptospirosis, Chikungunya, Zika. . .so it is
imperative what we do a rapid diagnosis. Often we use NS1 for
dengue diagnosis.”
Another important point raised by the experts was that indi-
viduals with DF may have low levels of NS1 which posed a risk of
a false negative result. Furthermore, the levels of NSI may differ
among individual patients and it was suggested that more studies
are undertaken to identify other more indicative biomarkers, espe-
cially for patients with severe dengue which could be fatal if not
properly managed.
“Currently, the dengue diagnostic is highly specific for detection
of the NS1 biomarker, but the biomarker [levels] differ. . .some
individuals express these proteins but at low level. In severe
dengue, some critical biomarkers go up such as biomarkers
related to intravascular leakage; if we can detect these biomark-
ers going up, doctors can immediately intervene. . .”
“Some patients NS1 may be very low and cannot be detected. . .
patients with secondary dengue often have low NS1 response
compared to those with primary dengue. . .”
There was also an opinion that the biomarkers of progression
to severe dengue are not fully understood and that controversy
regarding the cut-off criteria for some markers has resulted in
serious disagreement among clinicians, as illustrated in the quote
below.
“For instance, some papers suggested that higher viral load
increases the risk for severe dengue, but there is not a cut-off
point. Further, [diagnosis is] not based on one test, you need to
take [the cut-off point] along with other tests.”
195
Future prospects and opportunities
Experts believed there should be a shift of focus from detec-
tion of dengue in acute febrile cases to detection of impending
severe dengue among DF patients. The fact that dengue is com-
mon in tropical and subtropical countries, a majority of which
are developing countries with constraints on their financial and
technological resources which pose barriers to research and devel-
opment in dengue diagnosis especially on the detection of severe
dengue.
“Dengue diagnosis and test kits were developed in developed
countries, where dengue is not a problem. Little progress has
been made since the development of dengue test kits. Money
is needed for research and development; developed countries
may not want to fund the study of diseases in tropical countries
which is not a problem in their country. The market is not big
perhaps.”
Experts also stated that development of diagnostics for severe
dengue is not impossible, as there are many potential clinical
biomarkers that increase as a person develops dengue and pro-
gresses into severe dengue. Such biomarkers however, could be
examined further as potential diagnostic biomarkers for timely
recognition of progression to critical phases of the illness.
“When a person has dengue. . .intravascular leakage. . . There
are biomarkers in the blood. So, a diagnostic kit that is able to
identify these biomarkers will be useful. There are physiological
or haemostasis changes in those with severe dengue.”
“When a person has immunologic reactions in the body, there
are specific markers that will go up, definitely. . . . research has
not looked at it carefully because no research funds are being
given to do this.”
An expert observed that anti-dengue immune response varies
in individual patients, which means that identification of several
biomarkers may be helpful, as indicated in the quote below:
“There may not be one but several biomarkers, which is why we
have to look for several biomarkers, combined with some of the
well-established signs, such as haematocrit, ALT,. . .or possibly
dengue viral loads; you can take several together, or maybe give
a score, and you might be able to have a way to predict . . .a
signature for severe dengue.”
Rationale for developing a test for severe dengue
The experts were asked why tests to diagnose severe dengue
are important. Experts stated that a diagnosis of impending severe
dengue will help inform the decision for referral or admission of
a dengue patient into the hospital, especially in the case where a
patient may lack the typical clinical features of severe dengue and
could deteriorates rapidly. Having a test that could complement
a physician’s clinical assessment may also eliminate unnecessary
delays of severe dengue case management.
Secondly, the experts also expressed the opinion that if a test
for severe dengue becomes available it would help to reduce
costs, as the current methods for clinical diagnosis of severe
dengue (repeated clinical assessments, platelet counts, ferritin
test) are not only lengthy but costly. The availability of diagnos-
tics for severe dengue will also reduce unnecessary or avoidable
hospitalization and enable attentive management of dengue
patients.
196 P.-F. Wong et al. / Journal of Infection and Public Health 13 (2020) 193–198
Lack of hospital beds, especially during outbreak of epidemic
dengue, has been reported as the main reason to why dengue
patients could not be admitted into the hospital. Experts were
concerned especially of DF patients without overt warning signs
that are asked to return only if symptoms become severe as these
patients may develop severe dengue soon after and are late to come
to the hospital. Experts pointed out that a number of earlier studies
have suggested that many among those who succumbed to severe
dengue were brought late to the hospital. Availability of diagnostics
to determine who among those DF patients that are more likely to
develop severe dengue would enable the limited available beds in
the hospital to be appropriately allocated.
“Especially during dengue season. . . in dengue outbreaks, the
hospital will be swamped with dengue patients. We need a bet-
ter diagnosis so that we can clearly differentiate people who
are likely to develop severe forms of dengue and not send them
home.”
“It would be very helpful for patient management to know if it
will progress to severe dengue; it will be cost effective in terms
of getting the patient hospitalized or not.”
According to the experts, because diagnosis of severe dengue
is based on careful physician’s assessment of a combination of
clinical and laboratory findings, it is important that the attending
physicians have adequate training, experience and skills in recog-
nizing the typical course of illness for each of the clinical categories
of dengue and its respective appropriate management care. For
optimal management of plasma leakage, the correct type, volume
and duration of intravenous fluids; frequent assessments of vol-
ume and hydration status are essential in ensuring adequate fluid
replacement in patients with different plasma leakage rate. Simi-
larly, appropriate management of bleeding requires identification
of common sites of bleeding including the gastrointestinal tract and
recognition of other manifestations of bleeding such as menorrha-
gia in women, hematuria, and hemoptysis as well as recognition
that hematemesis and melena may be delayed in presentation. In
addition, early recognition of dengue complications such as liver
and kidney failure and encephalopathy would require initiation
or adjustment of treatment strategy [15]. Hence, clinical expertise
in recognizing the warning signs of severe dengue is critical for
appropriate clinical management to prevent fatalities.
“Diagnosis of severe dengue and caring for the patients is a very
challenging and long process; you need a doctor experienced
with the whole process. Not all doctors can do this, so it would be
good if there were a test for severe dengue instead of physician
judgement.”
“Patients can die depending on the doctor attending the patient.
Senior consultants who have seen many dengue patients are
all right, but in smaller hospitals where senior consultants
are not available, trainee doctors are left to attend these
patients; because these doctors are inexperienced in clinical
judgement. . . patients may die.”
“Especially in the areas where hospitals do not have many senior
consultants. . . if a severe dengue test was available, we imme-
diately could know this patient needed more care, and could
direct the patient to a bigger hospital.”
“. . .the doctors that see patients over the years develop good
clinical skills.”
Lastly, the experts believed that a lack of laboratory capacity in
rural healthcare settings to perform diagnostics essential for iden-
tification of severe dengue remains a challenge. Rural healthcare
facilities may not have the necessary equipment to undertake the
essential laboratory testing to detect DF and severe dengue.
“Not all hospitals can do a ferritin test, only bigger hospitals can
as it requires specialized equipment.”
“It is important for patients in rural communities to be diag-
nosed earlier so they can be referred to an expert earlier and
thus reduce complication.”
Important features of tests for severe dengue
Experts noted that due to the fluctuations of biomarker levels
in patients, several tests would likely be necessary to get accurate
representations with fast turnaround times of getting results, both
which are vital for the diagnosis of severe dengue. Experts desire
a rapid diagnostic test (RDT) akin to that of a pregnancy test kit,
where results could be obtained immediately, as expressed in the
quote below:
“. . .you’ll get the result immediately, it’s just like a preg-
nancy test. . .do the test and 10 minutes later it will develop a
reading. . .ideally, that would be the ideal kit. Dengue is an inter-
esting autoimmune disease, where sometimes the patient’s
condition can deteriorate rapidly, biomarkers change. . .every
few hours. . . therefore one needs to test several times.”
Experts also stated that a push towards the development of
severe dengue point-of-care (POC) diagnostics format is desired.
POC diagnostics will be exceptionally useful in rural settings where
there is a lack of laboratory facilities to conduct essential serological
tests for diagnosis of severe dengue. Furthermore, the diagnos-
tic challenges associated with autoimmune features caused by DF
would require POC diagnostics to facilitate immediate care and
treatment decisions.
When asked about the desired sensitivity of a test for severe
dengue, experts were of the opinion that the test should have sen-
sitivity of greater than 70%.
“Rapid diagnostic test sensitivity is about 70%, it is about 20 to
30 minutes. It is not as good as ELISA. . . the sensitivity. . .ELISA
is about 80–90%, depending on the brand of the kits, it would be
better if [the test] met par or was even better”
Discussion
To date, there is no routine laboratory diagnostic test for the
detection of severe dengue infection. Ability to diagnose impend-
ing severe dengue is vital for readiness of appropriate and effective
patient management regime. Close monitoring of patients could
prevent death from hypotensive shock, cardiorespiratory collapse
and cardiac arrest, which could occur within hours from the ini-
tial warning signs [16]. The major challenge identified by experts
was that the current diagnosis of severe dengue was not based on
a definitive test, as no such test exists. While diagnosing severe
dengue is performed empirically by physicians, low level of NS1
in some cases, varied clinical presentations, and controversy about
biomarker cut-off criteria could result in missed or delayed diag-
nosis and treatment. Furthermore, the similarity of symptoms and
pattern of presentation of dengue with other illnesses such as
malaria, leptospirosis and other febrile illnesses makes clinical
diagnosis more difficult and can often mislead the physicians [17].
The experts believed that there is an urgent need to address the
current challenges of diagnosis for severe dengue.
The experts in this study also mentioned the resources con-
straints faced by middle-income and developing countries, which
are also countries most impacted by dengue. In addition to the eco-
nomic burden, most of these countries may also lack the capacity
for research and development in which, evaluation of diagnostics,
preventives and therapeutics in an endemic area could provide
 P.-F. Wong et al. / Journal of Infection and Public Health 13 (2020) 193–198
findings of greater significance. In view of these limitations, more
funds should be devoted to research and development and to pro-
mote efforts in collaborating with other developed countries.
All the experts in this study are convinced that there is a
good potential for the development of diagnostic tests for severe
dengue, as there are already many potential prognostic biomark-
ers for severe dengue. As shown in several earlier studies, there
are various host immune, endothelial activation, biochemical, and
genetic markers which have potential utility as biomarkers for
severe dengue [18]. While studies evaluating important soluble
immune-modulating proteins such as IL-10 and IFN␥ yielded dis-
crepancies caused by varied sampling windows; TNF␣, proteases
and adhesion molecules have potential as alternative soluble prog-
nostic markers of severe dengue [19]. In particular, angiopoietin-2
and soluble VEGFR-2 were found strongly associated with clinically
apparent vascular leakage compared to the other factors associ-
ated with endothelial activation or dysfunction [20]. In addition,
the soluble form of CD163, a scavenger receptor expressed on
monocyte–macrophages which accumulates in the plasma upon
exposure to stimuli is increased in severe dengue patients com-
pared to those with mild dengue fever and is suggested as a
predictive marker for severe dengue [21]. These studies collectively
suggest that there is a significant potential for the development
of a diagnostics for severe dengue. More research focusing on the
identification of clinically useful, predictive biomarkers of severe
dengue and establishing their sensitivity and specificity hence are
needed.
During a dengue epidemic in most dengue endemic countries,
the volume of hospital admission is high and hospitals are con-
strained to admit only a limited number of patients. Unnecessary
admissions may be avoided through the use of predictive severe
dengue biomarkers diagnostics. In most countries where dengue
is endemic, dengue poses a substantial economic burden on the
healthcare system [22]. In Malaysia, dengue results in a combined
annual cost for prevention and illness of US$175.7 million [23].
The ability to diagnose patients with potential to develop severe
dengue will help in admission decisions and enable cost-effective
case management of dengue patients. In many dengue endemic
countries, the lack of laboratory diagnostic services and shortage
of clinical specialists are common especially in the rural areas [24],
further emphasizing the need for a severe dengue diagnostic test
in rural healthcare settings. As a specific diagnostic test for severe
dengue is currently unavailable, it will be essential to continue to
strengthen current dengue diagnosis and treatment facilities as a
way to curb the country’s rising rates of dengue fever morbidity
and mortality. There remains an urgent need to train physicians and
develop core competency in the management of patients suspected
of infection with dengue virus. Additionally, patients diagnosed
with dengue fever that do not need intensive case and are advised
on appropriate care at home should be educated to self-quarantine
at home.
Experts in this study noted some important desired features
of a diagnostic test for severe dengue. One of these features is a
fast turnaround time for results. Research should move towards
development of POC diagnostics for severe dengue. Interests in the
point-of-care tests (POCTs) for severe dengue reflect a need to ful-
fil requirements for not only frequent but also repeat screening as
biomarkers for severe dengue may change rapidly. More impor-
tantly, POCTs would be beneficial for dengue patients who were
sent home to monitor the progression of the illness as test could
be performed at any rural clinics. Having a POCT that could be
used as a home self-test kit could decrease the number of required
clinician–patient visits, which is particularly difficult for patients
who live far away from their health care provider. Patients would
be able to monitor the progression of their illness at home until they
become afebrile. The POCT hence, should be simple to use, simi-
197
lar to a pregnancy test kit. Furthermore, the experts also observed
that POCTs would be advantageous in rural health settings where
there is a lack of diagnostic services. The importance of POCTs in
improving healthcare accessibility and reducing delays in diagnosis
has been reported in previous study [25]. Furthermore, it is neces-
sary to enhance efforts in pursuing the development of clinically
relevant severe dengue biomarker with acceptable sensitivity and
specificity.
Limitations
Some weaknesses of this study were its small sample size and
qualitative approach, both of which reduce the generalizability of
results and limit our ability to draw firm conclusions. Despite these
limitations, data saturation has reached, and the authors believe
that because a range of expert backgrounds were represented in
the sample, the study has the advantage of diverse thoughts on
diagnosis of severe dengue from different perspectives.
Conclusion
In conclusion, findings from the study suggest that there is a
serious challenge faced by healthcare professionals in the diagno-
sis of severe dengue and an urgent need to address these challenges.
The development of a diagnostic test for severe dengue will be sup-
ported by healthcare professionals and should be pursued. A test
for severe dengue is needed due to the current challenges in clinical
judgement of progression to severe dengue, safe and cost-effective
management of severe dengue cases, avoidance of unnecessary
admissions, and the lack of clinical expertise and facilities for lab-
oratory diagnosis in rural healthcare settings. Experts observed
that there are great opportunities for development of a diagnos-
tic test for severe dengue, as many important biomarkers of severe
dengue have been identified that could be used for diagnosis. Future
research needs to focus on the development of a highly sensitive,
rapid test for severe dengue. This study outlines the directions for
future research and development of a severe dengue POC diagnos-
tics which is highly warranted for the purposes of diagnosis, patient
monitoring, and patient referrals.
Authors’ contributions
LPW, PFW and SAB conceived the study. LPW performed the
data collection and analyzed the data. PFW and SAB revised the
manuscript and gave approval of the version to be published. All
authors read and approved the final manuscript.
Funding
This study was supported by the Ministry of Energy, Sci-
ence, Technology, Environment and Climate Change (MESTECC),
Malaysia [FP0514B0025-2 (DSTIN), WP5C (GA019-2016)].
Conflict of interest
None declared.
Acknowledgement
We would like to thank all the experts who participated in this
study for sharing their views.
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