Journal of Infection (2017) xx, 1e3
www.elsevierhealth.com/journals/jinf
LETTER TO THE EDITOR
Cost effectiveness of screening for dengue
infection in a UK teaching hospital
KEYWORDS
Dengue;
Screening;
Serology;
PCR;
Cost-effectiveness
Dear Editor,
We note with interest the recent Letter from our
Singaporean colleagues describing dengue and Zika virus
co-infections.1 In the UK, such infections are mostly im-
ported,2 and our local testing involves sending samples to
a national reference laboratory, where the possibility of
co-infections are covered by a panel of tests covering
various viruses where infection presents with similar clin-
ical features, such as dengue, chikungunya and Zika virus.
We analysed the admission clinical and laboratory
parameters that were most closely associated with a pos-
itive diagnosis of acute dengue infection, in returning
travellers in a UK teaching hospital over a 3-year period
(2014e2016 inclusively), including the data from 173
patients (i.e. 2014: 43; 2015: 68; 2016: 62 patients).
The UK is not a dengue-endemic area so certain case
criteria are required to prompt a consideration of acute
dengue infection. These include: return from a country
where dengue is endemic, clinical features compatible with
dengue appearing within 3e10 days (more typically an
incubation period of 4e7 days), i.e. fever, rash, headache,
malaise, retro-orbital pain, myalgia and arthralgia.3 The
more severe haemorrhagic manifestations of dengue are
not seen in this patient cohort and the traditional tourni-
quet test is not usually performed during the routine clin-
ical examination of these patients.
Along with a compatible travel history and clinical
features we examined the admission haematology and
biochemical laboratory parameters and performed
http://dx.doi.org/10.1016/j.jinf.2017.09.006
0163-4453/ª 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Veater J, et al., Cost effectiveness of screening for dengue infection in a UK teaching hospital, J Infect
(2017), http://dx.doi.org/10.1016/j.jinf.2017.09.006
correlation statistics to investigate which of these variables
either singly or in combination were most accurately
associated with a diagnosis of acute dengue infection.
This was defined as the detection of dengue RNA by PCR,
the presence of dengue-specific IgM or documented dengue
IgG seroconversion. In addition, we included the requesting
team (general practitioners e GPs, general medicine, or
infectious diseases) as an additional parameter to include
in the correlation analysis.
The dengue virus testing was performed at the Rare and
Imported Pathogens Laboratory (RIPL) (Porton Down, Salis-
bury, UK). The main test options at the PHE RIPL reference
laboratory are either dengue IgG and IgM serology (if
presenting more than 5 days after symptom onset) and/or
dengue reverse-transcription polymerase chain reaction
(RT-PCR, if presenting within 5 days of symptom onset) e
NS1 antigen testing is not routinely offered. This test is a
routine geographical panel (including serology and PCR as
appropriate, for vector-borne pathogens), which is custom-
isable by the RIPL team according to patient travel and
clinical history, costing a flat rate of £148.30 per sample.4
Using a forward selection method in a logistic regression
model, we found that the platelet count (i.e. thrombocy-
topaenia, platelets <140
109/L, odds ratio 3.38, 95% con-
fidence limits 1.2e9.57; p Z 0.0217) was most closely
correlated with a diagnosis of dengue. The presence of
abdominal pain and vomiting were initially significantly
correlated with a diagnosis of dengue. However, the signif-
icance of these parameters was not sustained through the
logistic regression model. Similarly, a lower potassium
(Kþ) concentration, a higher alanine aminotransferase
(ALT), a lower albumin, and a lower total white cell count
(WCC) were also initially significantly correlated to dengue
infection, but these associations became non-significant af-
ter the logistic regression (Table 1). There was no signifi-
cant association between an accurate diagnosis of dengue
and the requesting team (Table 2).
The clinical features of dengue are well documented.
However these are non-specific and may not always be
present. There has been much research attempting to
identify patients with dengue who are most likely to
2 Letter to the Editor

Table 1 Symptoms and mean values of common laboratory results, on admission, in dengue-positive and dengue-negative
patient cohorts.
Symptom Dengue Not dengue p-Value
Number present % Number present %
Fever 19 90.5 115 76.2 0.169
Rigour 3 14.3 28 18.5 0.770
Rash 5 23.8 23 15.2 0.345
Retro-orbital pain 1 4.8 1 0.7 0.230
Headache 6 28.6 35 23.2 0.590
Photophobia 1 4.8 2 1.3 0.330
Neck stiffness 0 0 2 1.3 1
Myalgia 6 28.6 30 19.9 0.392
Arthralgia 3 14.3 17 11.3 0.716
Conjunctivitis 1 4.8 5 3.3 0.548
Sore throat 0 0 10 6.6 0.613
Abdominal pain 4 19 5 3.3 0.014
Diarrhoea 6 28.6 22 14.6 0.117
Vomiting 6 28.6 19 12.6 0.090
Anorexia 0 0 5 3.3 1
Cough 2 9.5 16 10.6 1

Laboratory results (units) [normal range] Mean SD Mean SD p-Value

Na (mmol/L) [133e146] 135.6 2.8 136.9 3.7 0.148
K (mmol/L) [3.5e5.3] 4 0.3 4.2 0.4 0.009
Urea* (mmol/L) [2.5e7.8] 5 4.2e6.8 4.55 3.7e6.1 0.302
Creatinine (mmol/L) [60e120] 85.8 47.1 76.7 33.6 0.415
Bilirubin (mmol/L) [0e21] 11.1 7.9 12.8 9.5 0.414
ALT* (IU/L) [2e53] 45 29e81 25.5 19e54 0.026
ALP* (IU/L) [30e130] 80 58e110 78 61e112 0.779
Albumin (g/L) [35e50] 40.5 4.2 42.5 4.1 0.050
Hb* (g/dL) [13.0e18.0] 132 15.9e138 125 15.1e141 0.685
WCC (
109/L) [4.0e11.0] 6.7 3.7 8.6 4.3 0.066
Platelets (
109/L) [140e400] 182.2 102.7 246.9 111.7 0.014
HCT (L/L) [0.400e0.540] 0.4 0 0.4 0.1 0.636
INR 1.1 0.1 1.1 0.2 0.363
PT (seconds) [11.0e14.0] 14.1 1.1 14.5 2 0.360
APTT 32.5 3.1 34 4.9 0.310
Other abbreviations: Na e serum sodium; K e serum potassium; ALT e alanine aminotransferase; ALP e alkaline phosphatase; Hb e hae-
moglobin; WCC e white cell count; HCT e haematocrit; INR e international normalised ratio; PT e prothrombin time; APTT e activated
partial thromboplastin time.
*Expressed as median and Q1eQ3; SD e standard deviation.

develop dengue shock syndrome.5,6 However, most of this
research is conducted on populations with endemic dengue,
raising the likelihood of a correlation due to the high pre-
test probability.
In travellers returning to the UK, we found no statisti-
cally significant correlation between any clinical features
and a positive diagnosis of dengue other than thrombocy-
topaenia. We argue that thrombocytopaenia is not unique
to dengue and its presence or absence in isolation would
not be enough to negate the need for serological testing.
The similar rates of correct diagnosis amongst general
medical doctors, general practitioners and infectious dis-
eases specialists suggests that even clinical experience in
assessing febrile travellers did not help with diagnosis e
again reflecting the non-specific clinical features of these
diseases.
Given that the differential diagnosis often includes more
dangerous pathogens, febrile returning travellers are often
admitted into isolation rooms in hospital - putting pressure
on hospital resources. Accurately diagnosing dengue infec-
tion allows for earlier de-escalation of infection prevention
measures, can save the cost of unnecessary further diag-
nostic testing, and potentially help in earlier discharge.
However, these benefits need to be weighed against the
cost of testing. In the period from 2014 to 2016, 173 tests
were performed, at a rate of £148.30 per test, for a total
cost of £25,656. Given that only 21 were positive for
dengue, the cost per diagnosis was £1222. However, 17 of
the tests identified a significant alternative pathogen. If
these are included the cost per diagnosis falls to £675, and
rate of positive diagnosis between the specialities increases
slightly but was not statistically significant (Table 2).

Please cite this article in press as: Veater J, et al., Cost effectiveness of screening for dengue infection in a UK teaching hospital, J Infect
(2017), http://dx.doi.org/10.1016/j.jinf.2017.09.006
Letter to the Editor 3

Table 2 Positive results for dengue and for any pathogen (including dengue) stratified by year and by requesting team.
Number Dengue % Dengue p-Value Any pathogen % Any pathogen p-Value
tested positive positive positive positive
Year
2014 43 5 11.6 10 23.3
2015 68 10 14.7 14 20.6
2016 62 6 9.7 14 22.6
Total 173 21 12.1 0.667 38 22.0 0.919
Requesting team
GP 33 2 6.1 7 21.2
IDU 52 8 15.4 15 28.8
*General medical 88 11 12.5 16 18.2
Total 173 21 12.1 0.434 38 22.0 0.338
*Including one request from each of Obstetrics and Occupational Health.
Abbreviations: GP e general practitioner; IDU e infectious diseases unit.

In conclusion, our data suggests that clinical features
and laboratory results are unable to exclude or diagnose
dengue infection in a febrile returning traveller, even when
they are assessed by a specialist in infection. The symptoms
of many other vector-borne pathogens are similarly non-
specific so similar arguments apply. Using a geographically-
based screening algorithm allows even a non-specialist to
reliably screen for a wide range of imported infections.
Clinicians should be aware that whilst such a screening
approach does not replace clinical specialist judgement
(most notably it would not exclude malaria or typhoid), it is
an extremely useful tool in the investigation of a febrile
returning traveller.
5. Yong YK, Tan HY, Jen SH, Shankar EM, Natkunam SK, Sathar J,
et al. Aberrant monocyte responses predict and characterize
dengue virus infection in individuals with severe disease. J
Transl Med 2017;15:121.
6. Thanachartwet V, Oer-areemitr N, Chamnanchanunt S,
Sahassananda D, Jittmittraphap A, Suwannakudt P, et al. Iden-
tification of clinical factors associated with severe dengue
among Thai adults: a prospective study. BMC Infect Dis 2015;
15:420.
James Veater
Nicholas Wong
Clinical Microbiology, University Hospitals of Leicester NHS
Trust, Leicester, UK

Authors’ declarations Florence Y. Lai

Department of Cardiovascular Sciences, University of
Leicester, Leicester, UK
This manuscript has not been submitted elsewhere for
publication. All authors have seen the final version of the NIHR Leicester Biomedical Research Centre, Glenfield
manuscript and are happy for it to be submitted for Hospital, Leicester, UK
publication. No funding was required for this case report.
Iain Stephenson
Martin Wiselka
Conflict of interest Infectious Diseases Unit, University Hospitals of Leicester
NHS Trust, Leicester, UK
None of the authors have conflicts of interest to declare.
Infection, Immunity, Inflammation, University of Leicester,
Leicester, UK
References
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Accepted 8 September 2017

Please cite this article in press as: Veater J, et al., Cost effectiveness of screening for dengue infection in a UK teaching hospital, J Infect
(2017), http://dx.doi.org/10.1016/j.jinf.2017.09.006