RESEARCH ARTI CLE Open Access

Spatial epidemiology and climatic predictors of

paediatric dengue infections captured via
sentinel site surveillance, Phnom Penh Cambodia
20112012
Andrew A Lover
1*
, Philippe Buchy
2
, Anne Rachline
3
, Duch Moniboth
4
, Rekol Huy
5
, Chour Y Meng
6
, Yee Sin Leo
7
,
Kdan Yuvatha
4
, Ung Sophal
8
, Ngan Chantha
5
, Bunthin Y
2
, Veasna Duong
2
, Sophie Goyet
3
, Jeremy L Brett
9
,
Arnaud Tarantola
10
and Philippe Cavailler
11
Abstract
Background: Dengue is a major contributor to morbidity in children aged twelve and below throughout
Cambodia; the 2012 epidemic season was the most severe in the country since 2007, with more than 42,000
reported (suspect or confirmed) cases.
Methods: We report basic epidemiological characteristics in a series of 701 patients at the National Paediatric
Hospital in Cambodia, recruited during a prospective clinical study (20112012). To more fully explore this cohort,
we examined climatic factors using multivariate negative binomial models and spatial clustering of cases using
spatial scan statistics to place the clinical study within a larger epidemiological framework.
Results: We identify statistically significant spatial clusters at the urban village scale, and find that the key climatic
predictors of increasing cases are weekly minimum temperature, median relative humidity, but find a negative
association with rainfall maximum, all at lag times of 16 weeks, with significant effects extending to 10 weeks.
Conclusions: Our results identify clustering of infections at the neighbourhood scale, suggesting points for
targeted interventions, and we find that the complex interactions of vectors and climatic conditions in this setting
may be best captured by rising minimum temperature, and median (as opposed to mean) relative humidity, with
complex and limited effects from rainfall. These results suggest that real-time cluster detection during epidemics
should be considered in Cambodia, and that improvements in weather data reporting could benefit national
control programs by allow greater prioritization of limited health resources to both vulnerable populations and
time periods of greatest risk. Finally, these results add to the increasing body of knowledge suggesting complex
interactions between climate and dengue cases that require further targeted research.
Background
Globally, dengue is the most widespread arbovirus, caus-
ing an estimated 390 million [95% Bayesian uncertainty
interval 284528] infections a year, of which only 96
million [67136] are captured via surveillance systems [1].
Dengue is endemic throughout Cambodia, one of the
poorest countries in Asia, which currently faces numerous
health challenges with limited health infrastructure and
poor economic indicators [2]. Morbidity from dengue is
extensive due to a range of interconnected factors, includ-
ing delays in care seeking, limited impacts of vector con-
trol, and limitations within the health sector [3,4].
Historically, large epidemics have occurred on a 34
year cycle, and generally all four dengue virus serotypes
circulate annually; DENV-2 and DENV-3 predominated
until recently, but have been largely displaced by DENV-1
since 2009 [5]. Dengue cases are reported throughout the
* Correspondence: [email protected]
1
Infectious Diseases Programme, Saw Swee Hock School of Public Health,
National University of Singapore, MD3, 16 Medical Drive, Singapore 117597,
Singapore
Full list of author information is available at the end of the article
2014 Lover et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.
Lover et al. BMC Public Health 2014, 14:658
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year, but with a sharp increase during the rainy season
(May to November).
A national syndromic surveillance program was estab-
lished in 1980, which includes passive reporting of clinically
diagnosed cases by public sector hospitals. Dengue is
included in the list of the 12 priority diseases that are
reported weekly to the Communicable Disease Control
Department of the Ministry of Health (MOH); this report-
ing system contains only aggregated data on new cases and
deaths for the diseases under syndromic surveillance. To
supplement this system, in 2001 the National Dengue
Control Program (NDCP) of the MOH implemented a
hospital-based surveillance in seven paediatric hospitals
or paediatric wards within referral hospitals. Weekly case
reporting from these sentinel hospitals includes basic
demographic indicators (age, gender, place of residence)
clinical findings on admission, and status at discharge. Sub-
sequently, this program was enhanced by the inclusion of
virological and serological surveillance at five sentinel hos-
pital sites. During the period 20022008, the National
Dengue Control Program (NDCP) has reported on average
103 cases per 100,000 with an annual case fatality rate
(CFR) ranging from 0.7 to 1.7% [3]. However, these sentinel
sites are not able to capture detailed epidemiological, clinical
or laboratory data, and reporting is generally incomplete; a
capture-recapture study in Cambodia indicated a 4- to 29-
fold underreporting rate [6]. The 2012 epidemic season was
the most severe in the country since 2007, with more than
42,000 suspect or confirmed cases reported, and serves to
highlight the serious epidemic potential within Cambodia.
To help address these limitations, our clinical study was
designed to capture comprehensive data for a prospective
series of paediatric dengue cases. The global objectives were
to fully explore the epidemiology and clinical spectrum of
clinical paediatric dengue in Cambodia; this portion of the
study examines the captured clinical cases within the larger
epidemiological context of spatial and climatic trends.
As a vector-borne disease, dengue transmission is in-
herently tied to weather patterns and climatic cycles,
and epidemics generally peak during the wet season, be-
ginning in the hot wet season from May-August, and
then tapering off through the cold wet season in
September. However, the fine-scale interactions of these
climatic conditions on Aedes vector populations are
poorly understood. Recent years have seen progressively
larger epidemics throughout Cambodia and SE Asia;
detailed spatial and epidemiological data are therefore
increasingly critical to maximize the effectiveness of
control programs within inherently limited budgets [7].
Methods
Sampling plan
Enrolment was organized weekly from September 20,
2011 to January 15, 2013 during specific surveillance days
in both the internal medicine and emergency wards of the
National Paediatric Hospital, Phnom Penh. All children
aged 115 years and presenting with fever, or history of
fever within seven days, on admission were screened for
eligibility criteria using the 1997 and the 2009 WHO den-
gue case definitions [8,9]. Informed consent was obtained
from parents or legal guardians for all eligible children.
Demographics and clinical data on admission and during
hospitalization were reported on a study-designed Case
Report Form (CRF). Paired sera were collected on admis-
sion and at discharge and shipped via courier the same
day for serologic (IgM Capture ELISA and haemagglutin-
ation inhibition assays) and virological (virus isolation on
2 cell lines, real time RT-PCR, and NS1 antigen detection
by commercial ELISA (BioRad)) tests for dengue and
other arboviral infections (i.e., Japanese encephalitis and
chikungunya) as reported previously [10]. Anonymized
data were entered into an electronic password-protected
database by a trained data manager, using Epi-Data 3.1
(Odense, Denmark) with range-checks; data monitoring
was performed by a clinician who checked the concord-
ance between the clinical notes, the study CRF and the
electronic files; discrepancies were then corrected in both
the CRF and the dataset.
Data sources
All clinical data in this study were collected by National
Paediatric Hospital staff (Phnom Penh) and all serololo-
gical and virological testing were performed at the
virology department of Institut Pasteur, Phnom Penh.
Temperature and humidity data were obtained for the
weather station in Phnom Penh [11], and precipitation
was obtained from satellite estimations [12]. Population
data and population density were obtained from pub-
lished reports from the Ministry of Statistics (2008) [13].
Approximately 60% of the 558 dengue-positive patients
resided in the greater Phnom Penh area; 216 patients
were geocoded to the sangkat (commune/urban village)
level. National-level reporting data was provided by the
National Dengue Control Program at the Ministry of
Health, Phnom Penh; open source base map layers were
obtained from Open Development Cambodia (March
2013), see http://www.opendevelopmentcambodia.net/
maps/downloads/.
Data analysis- regressions
Analysis of the relationship between weather events and
national reported disease counts utilized Poisson regres-
sion for over-dispersed data (negative binomial), and ex-
amined the time period January 2011 to January 2013. All
time-series models utilized Newey-West error correc-
tions for autocorrelated and heteroskedastic data [14].
Explanatory factors examined were the weekly mean, me-
dian, minimum, and maximum of available weather data,
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including temperature, relative humidity and rainfall, plus
the rainfall index defined as [(cumulative rainfall X days
with rainfall)/days in reporting period] [15]. Lag periods of
115 weeks were examined for all variables. Optimal
models were identified by Akaike information (AIC) and
Bayesian information (BIC) criteria; model fit was assessed
using standardized deviance residuals [16]. Stata 13.1
(College Station, Texas) was used for all analyses and all
tests were two-tailed, with = 0.05.
Data analysis- spatial
Visualization of captured cases data utilized ArcGIS 10.1
and QGIS 1.8 Lisboa. Detailed mapping and analysis in-
cluded only patients residing within greater Phnom Penh;
cases were geo-referenced to the centroid of the respective
sangkat (commune). Hot-spot detection used SaTScan
version 9.1 [17]; spatial and spatio-temporal clusters were
examined with Poisson models including the underlying
population density by commune. Bernoulli models were
not utilized due to the limited number of dengue-negative
patients. Clusters were limited to 25% of the total popula-
tion, and estimations used 999 replications for Monte
Carlo inference.
Ethics review
The study was conducted according to the ethical prin-
ciples of the Declaration of Helsinki of October 2002.
The Cambodian National Ethics Committee for Health
Research approved the overall study protocol after
institutional review (approval number 123-NECHR, 22
August 2011).
Results
From September 20, 2011 to January 15, 2013 a total of
1,228 febrile cases were admitted to the two participat-
ing wards. An eligibility form was completed for more
than 96% of these admissions (1,185/1,228); the propor-
tion of eligible patients was 59% (703/1,185) and the
study refusal rate was less than 1% (2/703). A total of
701 suspected dengue patients were enrolled during the
study period, and of these 80% (558/701) had a labora-
tory confirmation of dengue (Figure 1).
All four serotypes were identified during the study,
but DENV-1 predominated (520/558; 93%) (Table 1).
Our sentinel surveillance also detected a noteworthy
chikungunya outbreak reported in Cambodia in 2012: 7
patients had test results which were suggestive of recent
chikungunya infection [18,19]. However, no pathogens
were identified in the remaining patients.
Overall the proportion of under-5 children was 18%
(128/558) with an equal number of boys and girls. The
onset of fever prior admission was less or equal to three
days for 18% of subjects (126/558), and the median dur-
ation of hospital stay was 3 days. Overall, there were 5
deaths in the study population, indicating a case-fatality
rate of 0.7% (95% CI, 0.21.7%).
To assess the representativeness of our hospital cohort
relative to the national epidemic, we compared the weekly
caseload of admissions at the National Paediatric Hospital
with the figures reported nationally (Figure 2). While this
represents a crude proxy, the relationship is statistically
Fever or history of fever
N= 1,228
Eligibility forms
completed
n= 1,185
Eligibility forms
not completed
n= 43
Eligible for
inclusion
n= 703
Not eligible for
inclusion
n= 482
Enrolled
n= 701
Dengue (-)
n= 143
Refused
n= 2
Dengue (+)
n= 558
Figure 1 Patient inclusion flow, National Paediatric Hospital,
Phnom Penh, January 2011- January 2013.
Table 1 Results of the dengue serological and virological
testing (N= 701), National Paediatric Hospital, Phnom
Penh, September 2011 - January 2013
Diagnosis n % of total % of all dengue
positive or negative
(95% CI) (95% CI)
Positive dengue 558 79.6 -
(76.4 - 82.5)
Dengue 1 520 - 93.2
(90.8 95.1)
Dengue 2 8 - 1.4
(0.6 2.8)
Dengue 3 1 - 0.2
(0.005 1.0)
Dengue 4 2 - 0.4
(0.04 1.3)
Serotype unspecified 27 - 4.8
(3.2 7.0)
Negative dengue 143 20.4 -
(17.5 23.6)
Chikungunya 7 - 4.9
(2.0 9.8)
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significant across the study period when compared by
simple correlation (R
2
= 0.67; p < 0.001) and by time-series
regression (p < 0.001). These results indicate that the tem-
poral trends within the hospital and across Cambodia are
highly correlated and suggest that the admission trends in
cases captured in our study are indeed representative of
the national-scale dengue epidemic.
Two purely spatial clusters were identified (Figure 3). In
the first cluster, 46 cases were aggregated within the
southwest of the Phnom Penh suburban area over the en-
tire reporting period (RR = 2.12, no CI; p = 0.004). The
second cluster includes 43 cases aggregated in central
Phnom Penh (RR = 1.93, no CI; p = 0.031). These p-values
of less than 0.05 suggest these specific case aggregations
are unlikely to be due to chance. In spatio-temporal ana-
lysis, only a single large cluster (radius > 9 km) was found
to be marginally significant (p = 0.04) during October
2011 (data not shown). The standardized annual rates (per
100,000 population) within the city are shown as a choro-
pleth map in Figure 4; highest rates are evident in the
southwest and central regions, and these regions of high-
est risk coincide with the clusters identified in the spatial
analysis. To assess any biases in capture of patients with
geocoded addresses, the baseline demographics of patients
were compared to the overall study population, and no
significant differences were found (gender by rank-sum
test, p = 0.302; age by Kruskal-Wallis test, p = 0.063).
In the analysis of climatic impact on national dengue re-
ports, three examined variables had greatest explanatory
power in bivariate analysis: minimum weekly temperature;
median weekly relative humidity; and weekly maximum
rainfall (see Additional file 1: Table S1). The minimum
temperature was positively correlated with the number of
cases nationwide, with significant effects at lagged
intervals of 13, 6, and 911 weeks. The corresponding
incidence rate ratios (IRRs), ranging from 1.12 to 1.22, in-
dicate a 12-22% increase in cases per degree Celsius in-
crease in the weekly minimum temperature. The median
relative humidity was also positively correlated with den-
gue cases in multivariate models, having significant effects
at 13 weeks, with an IRR ranging from 1.036-1.042, indi-
cating a 4% increase in cases for each unit increase in the
weekly median relative humidity. Figure 5 illustrates the
general relationships between national reported cases and
significant climatic variables from multivariate analysis.
Among the examined rainfall variables, the maximum
weekly rainfall showed the strongest association with
reported dengue cases, with a positive correlation in
bivariate analysis. However, in multivariate analysis the
coefficients became negative, indicating an inverse rela-
tionship with dengue cases after adjusting for covari-
ates. Lag periods of 15, and 1012 weeks were all
significant, with IRRs ranging from 0.9910.987, indict-
ing a 0.91.3% decrease in cases per mm of rain per
week. Analysis of data from the other weather station in
Cambodia (Siem Reap; not shown) indicates the same
general multivariate trends, however these data are lim-
ited by extensive missing values.
Discussion
We present the results of a large prospective descriptive
study of paediatric dengue infection conducted in a single
referral centre in Phnom Penh, Cambodia. All 701 children
enrolled in the study were initially suspected as having
dengue, and nearly 80% included had a positive confirma-
tory test. The inclusion period was from September 2011
to January 2013, which covered two dengue epidemic sea-
sons. Although all four serotypes were found in circulation
during the period, DENV-1 predominated in 20122013;
these trends are consistent with data from the National
Surveillance system [5].
Spatial epidemiology has been specifically highlighted as
a key component to guide dengue control efforts, espe-
cially in resource-limited settings. A recent analysis of
large-scale transmission patterns of dengue in Cambodia
identified hotspots - zones of high transmission that may
serve as reservoirs of virus for subnational scale epidemi-
ology [20]. Extensive fever cohorts have found large differ-
ences in transmission within and between urban and rural
regions [21]; however, these studies did not address
neighbourhood-scale effects, which are dominated by hu-
man movements between neighbourhoods. The results
from this study show substantial heterogeneity of trans-
mission within Phnom Penh, mirroring larger scale infec-
tion dynamics within Cambodia. Our results suggest that
rapid identification and targeting of these areas could have
important impacts on transmission, especially in areas of
high population density.
0
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Epidemic week
National reporting
Total admissions, National Paediatric Hospital
Study inclusions
Figure 2 Comparison of national reporting data versus hospital
inpatient cases, National Paediatric Hospital, Phnom Penh
September. 2011- January 2013. Note: (p < 0.001, time-series
regression of total hospital admissions and national cases).
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When examined as total cases per population for the
study period, we identified several areas of elevated risk
in the southwest and central areas of Phnom Penh ag-
gregated over the course of this study. Such clusters
could be high-risk areas for dengue epidemics due to
larval sites or other modifiable characteristics and
should be prioritized for vector control activities includ-
ing community health promotion & education, elimin-
ation of breeding sites, water treatment using larvicides,
and isolation of fever cases. Recent large-scale studies
conducted in Bangkok found long-term modulation of
transmission based on population-level (herd) immun-
ity at the neighbourhood scale [22]; our study findings
are consistent with these results. The overwhelming pre-
dominance of a single serotype, however, hindered inves-
tigation of serotype-specific clusters and any potential
interactions on population immunity.
The time lags identified within this study are broadly
consistent with those found in other locations within SE
Asia: in Thailand lag times of 6 months for temperature
maxima and 3 months for rainfall events were identified; in
Singapore, lag times of 15 months for mean temperature
and rainfall events were identified [23,24]. In common with
studies in Sri Lanka and New Caledonia, we find very lim-
ited and complex impact of rainfall on dengue incidence
[25,26]. A main limitation is that the rainfall data are de-
rived from satellite imagery, and may have limited spatial
and temporal accuracy. However, satellite imagery in gen-
eral has been shown to be most accurate for low latitudes
during the warm season [27], suggesting that these esti-
mates are likely reasonable. Additional support for this in-
terpretation is the finding of an inverse relationship
between rainfall and Aedes larval densities in Malaysia,
suggesting a flooding-out of larval habitats during periods
of extreme rainfall [28]. These results concur with recent
studies that found complex non-linear interactions be-
tween climatic variables and dengue incidence [29].
Limitations of this study
These data have been collected in a single referral paediat-
ric hospital in Phnom Penh during a limited period of
time, and therefore our findings may not be representative
of other areas with different dengue transmission patterns,
populations or population density characteristics. Cases
from the spatiotemporal analyses were limited to those
cases with an address that could be geo-referenced; some
DENV-1
DENV-2
DENV-4
DENV, serotype ND
0 10 km
DENV-3
Case cluster 1
Case cluster 2
Figure 3 Mapping of cases by serotype showing significant spatial clusters within greater Phnom Penh, by smallest administrative
district (sangkat) (n = 216). Note: Cluster 1 (radius- 5.2 km): 46 cases; relative Risk = 2.1 (p = 0.004); Cluster 2 (1.7 km): 43 cases; relative
Risk = 1.9 (p = 0.031).
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patients provided the name of an older administrative
system that could not be readily mapped; however, this
bias would have led to omission of cases This would
not impact cluster detection with underlying popula-
tion values as any impacts would be expected to dilute
the observed effect sizes. There were no significant dif-
ferences in age or gender between captured patients
and those without addresses, suggesting there was no
differential loss to follow-up.
There is also the potential for bias in our results due
to differences in care-seeking behaviour. Patients are
likely to seek care at the closest referral centre, which
may partially explain the clustering of the cases in this
study within Phnom Penh. However, as the hospital
serves as the main paediatric referral centre within the
public sector, this bias is likely minor.
We have also used a single set of weather data to pre-
dict the national scale epidemic. The local-scale interac-
tions between climate, vectors and people - that is, the
micro-epidemiology and heterogeneous exposures - can-
not be captured at this scale [30].
0 to 5
0 10 km
> 5 to 17
> 17 to 33
> 33 to 61
Figure 4 Mapping of cases as annual population standardized rates per 100,000 total population (2008 population estimates) by
smallest administrative district (sangkat) (n = 216).
0
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Epidemic week
Cases RH median,% Temp min.,
O
C Rain max.,mm
Figure 5 Comparison of national reporting data and significant
climatic variables, Cambodia national data, December 2010-
December 2012. Note: RH = relative humidity.
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Bearing these limitations in mind, our analysis shows a
very strong correlation between observed trends and na-
tional dengue data trends as well as a strong correlation
between local rainfall and temperature data and satellite
estimates at the national level.
Conclusions
From an operational standpoint, the monitoring of peak
temperatures, extreme humidity and rainfall indexes could
help prioritize resources to be mobilized to address any
emerging transmission cycles; however, the lead times
identified in these data of 16 and 910 weeks might not
provide sufficient time to implement aggressive campaigns
in a resource-limited setting like Cambodia. Our results
also suggest that a wider range of weather summary in-
dexes should be incorporated into models to improve
model fit and prediction. Recent work in malaria also sug-
gests that predictions may be improved by using high-
resolution data instead of traditional regional and weekly
summaries [31], and surveillance in Cambodia could
benefit from improved weather reporting systems.
While the routine use of environmental variables for
real-time dengue surveillance can be complex in real-
world settings [32], the wide availability of open-source
tools (QGIS, R software and SaTScan) [17,33,34] make
this increasingly feasible even in resource-limited settings.
These results can serve as a foundation for the implemen-
tation of robust real-time surveillance within Cambodia.
Finally, the ability to pre-plan and stockpile needed re-
sources (control staff, Bti, etc.) should be considered [35],
and the identification of multiple hotspots of higher risk
relative to the remainder of Phnom Penh suggests areas
that should targeted for enhanced surveillance and vector
control efforts during future transmission seasons.
Additional file
Additional file 1: Table S1. Time series negative binomial regression
for reported national dengue cases, Cambodia, Dec. 2010- Dec. 2012.
Competing interests
JLB is a paid employee of Sanofi Pasteur; YSL was a medical advisor for
Sanofi Pasteur; all other authors declare that they have no conflicts of
interest.
Authors contributions
JB assisted in the design of the overall clinical study; all other authors
participated in conceptualizing the design and coordination/data collection
of the overall clinical study. AAL and PC conceived, planned, and analysed
the data for this analysis and wrote the first draft; all authors read and
approved the final manuscript.
Acknowledgements and funding
We are grateful for both the patients and their families for agreeing to take
part in this study, and for the critical contributions of the staff and nurses at
the National Paediatric Hospital, without which this study would not have
been possible. We are also grateful for the assistance of Julien Cappelle
(Institut Pasteur, Cambodia) for his assistance in bulk downloading of
weather data. The rainfall data used in this study were acquired using the
GES-DISC Interactive Online Visualization ANd aNalysis Infrastructure
(Giovanni) as part of the NASAs Goddard Earth Sciences (GES) Data and
Information Services Center (DISC).
Funding for this study was provided by Sanofi-Pasteur. The sponsors of
the study were involved in study design and review of the manuscript; the
sponsors had no role in the data collection/analysis and the decision to
publish was made jointly by all authors.
Author details
1
Infectious Diseases Programme, Saw Swee Hock School of Public Health,
National University of Singapore, MD3, 16 Medical Drive, Singapore 117597,
Singapore.
2
Virology Unit, Institut Pasteur in Cambodia, Phnom Penh,
Cambodia.
3
Formerly- Regional Emerging Diseases Intervention (REDI)
Centre, Singapore, Singapore.
4
Infectious Diseases Unit, National Paediatric
Hospital, Phnom Penh, Cambodia.
5
National Dengue Control Program
(NDCP), National Center for Parasitological, Entomology and Malaria Control,
Ministry of Health, Phnom Penh, Cambodia.
6
Ministry of Health, Phnom
Penh, Cambodia.
7
Tan Tock Seng Hospital, Centers for Disease Control,
Singapore, Singapore.
8
Emergency Unit, National Paediatric Hospital, Phnom
Penh, Cambodia.
9
Medical Affairs Department, Sanofi Pasteur, Singapore
Regional Office, Singapore, Singapore.
10
Epidemiology Unit, Institut Pasteur
in Cambodia, Phnom Penh, Cambodia.
11
Mdecins Sans Frontires,
Operational Centre, Geneva, Switzerland.
Received: 19 January 2014 Accepted: 20 June 2014
Published: 28 June 2014
References
1. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM,
Brownstein JS, Hoen AG, Sankoh O, Myers MF, George DB, Jaenisch T, Wint
GRW, Simmons CP, Scott TW, Farrar JJ, Hay SI: The global distribution and
burden of dengue. Nature 2013, 496:504507.
2. United Nations Development Programme: Human Development Report. New
York; London: United Nations; Eurospan; 2013.
3. Huy R, Buchy P, Conan A, Ngan C, Ong S, Ali R, Duong V, Yit S, Ung S, Te V,
Chroeung N, Pheaktra NC, Uok V, Vong S: National dengue surveillance in
Cambodia 19802008: epidemiological and virological trends and the
impact of vector control. Bull World Health Organ 2010, 88:650657.
4. Beaut J, Vong S: Cost and disease burden of dengue in Cambodia.
BMC Public Health 2010, 10:521.
5. Dengue situation in Cambodia, 2012 update (National Dengue Control
Programme). http://www.cnm.gov.kh/userfiles/file/Annual%20Report%
202012/19_Dengue_CNM_%20Situation_2012.pdf.
6. Vong S, Goyet S, Ly S, Ngan C, Huy R, Duong V, Wichmann O, Letson GW,
Margolis HS, Buchy P: Under-recognition and reporting of dengue in
Cambodia: a capturerecapture analysis of the National Dengue
Surveillance System. Epidemiol Infect 2012, 140:491499.
7. Eisen L, Lozano-Fuentes S: Use of mapping and spatial and space-time
modeling approaches in operational control of Aedes aegypti and
dengue. PLoS Negl Trop Dis 2009, 3:e411.
8. World Health Organization: Guidelines for Treatment of Dengue Fever /
Dengue Haemorrhagic Fever in Small Hospitals. New Delhi: WHO Regional
Office for South-East Asia; 1999.
9. World Health Organization: Dengue Guidelines for Diagnosis, Treatment,
Prevention and Control. Geneva: World Health Organization; 2010. New edition.
10. Andries A-C, Duong V, Ngan C, Ong S, Huy R, Sroin KK, Te V, Y B, Try PL, Buchy P:
Field evaluation and impact on clinical management of a rapid diagnostic
kit that detects dengue NS1, IgM and IgG. PLoS Negl Trop Dis 2012, 6:e1993.
11. Integrated Surface Database (ISD) | National Climatic Data Center (NCDC). http://
www.ncdc.noaa.gov/land-based-station-data/integrated-surface-database-isd.
12. TRMM Multi-Satellite Precipitation Data. http://disc2.nascom.nasa.gov/
Giovanni/tovas/TRMM_V7.3B42_daily.2.shtml.
13. General Population Census 2008. http://celade.cepal.org/khmnis/census/khm2008/.
14. Newey WK, West KD: A simple, positive semi-definite, heteroskedasticity
and autocorrelation consistent covariance matrix. Econometrica 1987,
55:703708.
15. Russell PF, West LS, Manwell RD: Practical Malariology. Philadelphia: W. B.
Saunders; 1946.
16. Dupont WD: Statistical Modeling for Biomedical Researchers. 2nd edition.
Cambridge, New York: Cambridge University Press; 2009.
Lover et al. BMC Public Health 2014, 14:658 Page 7 of 8
http://www.biomedcentral.com/1471-2458/14/658
17. Kulldorff M, Information Management Services, Inc: SaTScan. 2011. Software
for the Spatial and Space-Time Scan Statistics, http://www.satscan.org/.
18. Duong V, Andries A-C, Ngan C, Sok T, Richner B, Asgari-Jirhandeh N,
Bjorge S, Huy R, Ly S, Laurent D, Hok B, Roces MC, Ong S, Char MC,
Deubel V, Tarantola A, Buchy P: Reemergence of chikungunya virus in
Cambodia. Emerg Infect Dis 2012, 18:20662069.
19. Centers for Disease Control and Prevention (CDC): Chikungunya outbreak
Cambodia, February-March 2012. MMWR Morb Mortal Wkly Rep 2012,
61:737740.
20. Teurlai M, Huy R, Cazelles B, Duboz R, Baehr C, Vong S: Can human
movements explain heterogeneous propagation of dengue fever in
Cambodia? PLoS Negl Trop Dis 2012, 6:e1957.
21. Vong S, Khieu V, Glass O, Ly S, Duong V, Huy R, Ngan C, Wichmann O,
Letson GW, Margolis HS, Buchy P: Dengue incidence in urban and rural
Cambodia: results from population-based active fever surveillance,
20062008. PLoS Negl Trop Dis 2010, 4:e903.
22. Salje H, Lessler J, Endy TP, Curriero FC, Gibbons RV, Nisalak A, Nimmannitya
S, Kalayanarooj S, Jarman RG, Thomas SJ, Burke DS, Cummings DAT:
Revealing the microscale spatial signature of dengue transmission and
immunity in an urban population. PNAS 2012, 109:95359538.
23. Hii YL, Rocklv J, Wall S, Ng LC, Tang CS, Ng N: Optimal lead time for
dengue forecast. PLoS Negl Trop Dis 2012, 6:e1848.
24. Focks DA, Barrera R: Dengue Transmission Dynamics: Assessment and
Implications for Control. In WHO Report of the Scientific Working Group
meeting on Dengue, Geneva. Geneva: Working paper for the Scientific
Working Group on Dengue Research, convened by the Special Programme
for Research and Training in Tropical Diseases; 2006. http://www.who.int/
tdr/publications/publications/swg_dengue_2.htm.
25. Goto K, Kumarendran B, Mettananda S, Gunasekara D, Fujii Y, Kaneko S:
Analysis of effects of meteorological factors on dengue incidence in Sri
Lanka using time series data. PLoS One 2013, 8:e63717.
26. Descloux E, Mangeas M, Menkes CE, Lengaigne M, Leroy A, Tehei T,
Guillaumot L, Teurlai M, Gourinat A-C, Benzler J, Pfannstiel A, Grangeon J-P,
Degallier N, De Lamballerie X: Climate-based models for understanding
and forecasting dengue epidemics. PLoS Negl Trop Dis 2012, 6:e1470.
27. Ebert EE, Janowiak JE, Kidd C: Comparison of near-real-time precipitation
estimates from satellite observations and numerical models. Bull Am
Meteorol Soc 2007, 88:4764.
28. Wee LK, Weng SN, Raduan N, Wah SK, Ming WH, Shi CH, Rambli F, Ahok CJ,
Marlina S, Ahmad NW, Mckemy A, Vasan SS, Lim LH: Relationship between
rainfall and Aedes larval population at two insular sites in Pulau Ketam,
Selangor, Malaysia. Southeast Asian J Trop Med Public Health 2013, 44:157166.
29. Hii YL, Zhu H, Ng N, Ng LC, Rocklv J: Forecast of dengue incidence using
temperature and rainfall. PLoS Negl Trop Dis 2012, 6:e1908.
30. Smith DL, Dushoff J, McKenzie FE: The risk of a mosquito-borne infection
in a heterogeneous environment. PLoS Biol 2004, 2:e368.
31. Weiss DJ, Bhatt S, Mappin B, Boeckel TPV, Smith DL, Hay SI, Gething PW: Air
temperature suitability for Plasmodium falciparum malaria transmission
in Africa 20002012: a high-resolution spatiotemporal prediction.
Malar J 2014, 13:171.
32. Racloz V, Ramsey R, Tong S, Hu W: Surveillance of dengue fever virus: a
review of epidemiological models and early warning systems. PLoS Negl
Trop Dis 2012, 6:e1648.
33. QGIS Development Team: QGIS Geographic Information System. Open Source
Geospatial Foundation Project. 2013. http://qgis.osgeo.org.
34. R Core Team: R: A Language and Environment for Statistical Computing.
Vienna, Austria: Foundation for Statistical Computing; 2013.
35. Conolly MA: World Health Organization: Communicable Disease Control in
Emergencies: A Field Manual. Geneva: World Health Organization; 2005.
doi:10.1186/1471-2458-14-658
Cite this article as: Lover et al.: Spatial epidemiology and climatic
predictors of paediatric dengue infections captured via sentinel site
surveillance, Phnom Penh Cambodia 20112012. BMC Public Health
2014 14:658.
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