Trans R Soc Trop Med Hyg 2020; 0: 1–10

doi:10.1093/trstmh/traa030 Advance Access publication 0 2020

Spatiotemporal evolution of dengue outbreaks in Brazil

ORIGINAL ARTICLE
∗,†,b
Thiago S. de Azevedo†,a , Camila Lorenz , and Francisco Chiaravalloti-Netob

a
Secretary of Health, Municipality of Santa Barbara d’Oeste - Santa Bárbara d´Oeste, 13450-021, Sao Paulo, Brazil; b Department
of Epidemiology, School of Public Health, Universidade de São Paulo, 01246-904, Sao Paulo, Brazil
∗ Corresponding author: Tel: +55(11)30617920; E-mail: camilalorenz@usp.br

† These authors contributed equally.

Received 26 June 2019; revised 3 October 2019; editorial decision 12 April 2020; accepted 22 April 2020

Background: Dengue is a mosquito-borne febrile disease infecting millions of people worldwide. Identification
of high-risk areas will allow public health services to concentrate their efforts in areas where outbreaks are most
likely to occur. The present study focuses on describing the spatiotemporal evolution of dengue outbreaks in
Brazil from 2000 to 2018.
Method: To assess the pattern behaviour and spatiotemporal trend of dengue outbreaks, the non-parametric
kernel estimator method and the Mann–Kendall test, respectively, were used. Bivariate global Moran’s I statistic
was used to test the spatial correlation between dengue outbreaks, temperature, precipitation and population
data.
Results: Our results revealed that the transmission cycles of dengue outbreaks vary in different spatiotemporal
scenarios, with intermittent periods of outbreaks. In the period of study, outbreak clusters were primarily con-
centrated in the Northeast region and the transmission of dengue extended throughout Brazil until 2018. The
probability of occurrence of dengue outbreaks was higher in high temperatures. Further, these space-time fluc-
tuations in the number of outbreaks in the different regions were probably related to the high mobility between
the populations of these regions, circulating serotypes and susceptible populations.
Conclusions: The distribution of dengue outbreaks is not random; it can be modified by socioeconomic and
climatic moving boundaries.

Keywords: Brazil, dengue outbreak, Mann–Kendall analysis, non-parametric kernel estimator method

Introduction
Dengue is a flaviviral disease caused by four serotypes of dengue
virus (DENV 1–4), which are vectored mainly by Aedes aegypti
and Aedes albopictus mosquitoes.1 This vector-borne disease is
the most prevalent in the Americas and the second most preva-
lent globally; there are about 50–100 million new dengue cases
in tropical and subtropical regions annually.2 It is estimated that
about 3.9 billion people are at risk of dengue infection worldwide
each year.3 In 2016, 802 249 new cases of dengue fever were
reported in Brazil alone, affecting all regions except the South.4
Many municipalities have climatic and socioeconomic conditions
that are conducive to the proliferation and vectorial capacity of
A. aegypti and, consequently, dengue outbreaks.
The rapid development of geographic information systems
(GISs) has led to an increase in the importance of spatial data
analysis in infectious disease epidemiology.5,6 Mosquito-borne
diseases are usually clustered in high-risk areas7 ; thus, the recog-
nition of these high-risk areas can support surveillance and con-
trol measures by focusing expenditure of limited resources where
they are most likely to have an impact. Dengue transmission, in
particular, shows dynamic spatiotemporal patterns because of
the variable environment and different immunological profiles
of the population.5 This characteristic non-homogeneous and
unstable distribution of potentially important predictors makes
it difficult to assign epidemiological changes to specific factors.
Despite complexities, an analysis of the distribution of dengue
outbreaks can be helpful in determining the spatiotemporal dis-
tribution of dengue.7 In Brazil, recognition of high-risk areas will
allow public health services to concentrate their efforts toward
areas where outbreaks are most likely to occur.
In light of this situation, in this study, we analysed the spa-
tiotemporal distribution of dengue fever outbreaks that occurred

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1
T. S. de Azevedo et al.
Figure 1. Map of Brazil showing the states belonging to each
region. Acronyms for each state: Acre—AC; Alagoas—AL; Amapá—
AP; Amazonas—AM; Bahia—BA; Ceará—CE; Distrito Federal—DF; Espírito
Santo—ES; Goiás—GO; Maranhão—MA; Mato Grosso—MT; Mato Grosso
do Sul—MS; Minas Gerais—MG; Pará—PA; Paraíba—PB; Paraná—PR;
Pernambuco—PE; Piauí—PI; Roraima—RR; Rondônia—RO; Rio de
Janeiro—RJ; Rio Grande do Norte—RN; Rio Grande do Sul—RS; Santa
Catarina—SC; São Paulo—SP; Sergipe—SE; Tocantins—TO. Modified from
IBGE.
in Brazil from 2000 to 2018. For this purpose, the areas that were
most susceptible to the occurrence of this arbovirus were identi-
fied by means of a GIS and principles of geostatistics. We aimed
to identify clusters with different dengue risks and to determine
whether the spatiotemporal pattern of dengue has changed in
Brazil over a 19-y period. Further, we have interpreted the results
to promote more efficient risk-based dengue surveillance.
Materials and methods
Brazil is a South American country politically divided into five
regions and 27 administrative states (Figure 1) composed of 5570
municipalities. Data used in the analyses were obtained from
the Brazilian Ministry of Health8 and included annually reported
autochthonous cases of dengue from 2000 to 2018, distributed
throughout Brazil. Subsequent analyses followed the same pro-
cedures as described by Azevedo and Sallum.9 The incidence of
cases was calculated on the basis of the information provided
by Fotheringham et al.10 ; thus, the municipalities that underwent
outbreaks of the disease were determined. We consider the out-
break definition proposed by Brady et al.:11 ‘outbreak years within
the base dataset were defined by the total annual number of
cases exceeding two standard deviations of any combination of
three or more historical years’. The historical average of the dis-
ease incidence for the period from 2000 to 2018 and the stan-
dard deviations were calculated. Thus, those municipalities that
presented an incidence value higher than the stipulated endemic
threshold were considered to have had an outbreak.
2
The non-parametric kernel estimator method was used for
the estimation of density functions of the dengue outbreak pat-
tern behaviour.10 Using this estimator, it was modified to a two-
dimensional function on the dengue outbreaks, comprising a
surface whose value was proportional to the intensity of the
samples per unit area. To determine the radius of influence,
measured in decimal degrees, a spatial autocorrelation method
was deployed utilising a geostatistical tool, the semivariogram,
which calculates the arithmetic means of the square of the dif-
ferences of a set of pairs of events within a region in a given
direction separated by distance. The semivariograms express the
spatial behaviour of the variables by analysing the degree of
spatial dependence between the samples within an experimen-
tal field and thus determine the radius of influence around the
samples.
To assess the spatiotemporal trend of increasing or decreas-
ing incidence of dengue outbreaks, we used the Mann–Kendall
test.12,13 The statistical variable S for a series of n data from the
Mann–Kendall test is calculated from the sum of the sign (sgn) of
the difference, in pairs, of all values of the series (xi) in time t with
respect to the values at t + 1 (xj), expressed in equations (1) and
(2).

n−1 
n
S= sgn(x j − xi ) (1)
i= j j=i+1
⎧
⎪ +1; se x j > xi
⎨
sgn(x j − xi ) = 0; se x j = xi (2)
⎪
⎩
−1; se x j < xi
This method requires that the variables be independent and
random; hence, the Mann–Kendall Contextual (CMK) test was
performed.14 This calculation was used because geographically
neighbouring regions tend to have similar characteristics. How-
ever, the Mann–Kendall test is performed individually on each
pixel, not considering the behaviour of neighbouring pixels. The
CMK method is non-parametric and consists of regionalisation of
the series. It is necessary to consider the magnitude of autocor-
relation on significance testing. For this procedure, we applied a
mask of the average of the pixels with the dimensions of ‘3 × 3’
after calculation of the variable ‘S’ from the Mann–Kendall test.
This grid size was used because it was the best fit to the semi-
variogram results, i.e. the influence area of the kernel estima-
tor was approximately 3 × 3 pixels. The data were compiled and
analysed using the Idrisi Selva 17.02 GIS (Clark Labs, Worcester,
Massachusetts, USA). The Earth Trends Modeler module was used
to analyse trends in the spatially distributed historical series. The
final result of this analysis was a map showing the estimated spa-
tiotemporal trend, which allowed us to observe changes in the
disease’s behaviour and determine which regions have experi-
enced significant changes in incidence over time.
Spatial correlation analyses were performed in Geoda 0.9
software (Center for Spatially Integrated Social Science, Illinois,
USA). Spatial correlation can be detected through global or local
measures. Moran’s I spatial autocorrelation statistic was calcu-
lated to determine whether spatial clustering was a feature of
Transactions of the Royal Society of Tropical Medicine and Hygiene
Figure 2. Historical evolution of dengue outbreaks in Brazil from 2000 to 2018. The red arrows indicate the years with the highest number of munici-
palities that registered outbreaks.
dengue in our 19-y study period. Moran’s I ranges from −1 to 1
and can be interpreted as follows: a value close to 0 indicates
spatial randomness, while a positive value indicates positive
spatial autocorrelation and a negative value indicates nega-
tive spatial autocorrelation.5 The Moran indices were calcu-
lated by means of a neighbourhood-matrix W, applying the
same approach as Hu et al.5 and Castillo et al.15 In order to
obtain W, the criterion of ‘common border’ is used, in which
research areas with a common border are considered neigh-
bours. Local indicators of spatial association (LISA) analysis was
used to identify high-high and low-low groups of municipalities
(referred to as spatial clusters). High-high refers to municipali-
ties with high dengue incidence that are surrounded by neigh-
bouring municipalities with high dengue incidence and low-low
refers to municipalities with low dengue incidence that are sur-
rounded by neighbouring municipalities with low dengue inci-
dence: these are indicative of positive spatial autocorrelation.5
Bivariate local and global Moran’s I statistics were used to identify
spatial correlations between dengue outbreaks with climatic vari-
ables and population data. Temperature and precipitation data
were obtained from WorldClim16 representative of the last 50 y
(measured monthly) and interpolated at a resolution of 30 arc-s
(approximately 1 km). Population data for each municipality were
obtained from the Instituto Brasileiro de Geografia e Estatística
(IBGE) 2010 Population Census.17 The statistical significances of
Moran indices were calculated from the permutation distribution
(999) of the value for other areas, until obtaining a pseudo dis-
tribution (p) for which the parameters of significance could be
computed. These parameters were calculated from 999 random
permutations of Moran I values from the correlation of dengue
outbreaks.
Results
During the period from 2000 to 2018, Brazil recorded dengue out-
breaks in several municipalities. Since the beginning of transmis-
sion, the greatest outbreaks occurred in 2010, 2013 and 2015
(Figure 2).
Figure 3 depicts the geographic distribution of kernel esti-
mates of dengue outbreaks in Brazil in this 19-y period. It shows
that the occurrence of outbreaks varied geographically across
the country and that dengue has been expanding its trans-
mission area across almost the entire Brazilian territory, con-
solidating as hyperendemic along the east coast and the cen-
tral regions. The incidence rates of each municipality can be
seen in Supplementary Figure 1. Even with this variation, it is
possible to notice that the largest number of outbreaks was
always concentrated in the Northeast, Southeast and Central-
West regions of the country. Before 2006, the vast majority of
dengue outbreaks were in northeastern municipalities. By 2006,
there was an increase in dengue outbreaks in the Southeast
and Midwest. Variographic analysis showed two distinct patterns:
one from 2000 to 2004 (C—C0 < 0.005) and the other from
3
T. S. de Azevedo et al.
Figure 3. Kernel estimator method of dengue outbreak pattern behaviour in Brazil from 2000 to 2018. The red areas represent where the outbreaks
are concentrated.
2005 to 2018 (C—C0 > 0.008), mainly because of the nugget
effect (Supplementary Figures 2 and 3). The nugget effect is a
geostatistical term used to describe the variability seen between
samples that are closely spaced. From 2000 to 2004 outbreaks
were geographically restricted; there was little spatial correlation
between them. However, it is possible to observe that the munici-
palities which experienced outbreaks had high spatial correlation
after 2005.
The Mann–Kendall analysis showed how the occurrence of
outbreaks changed in each area over time (Figure 4). Both positive
(increased number of outbreaks) and negative (decreased num-
ber of outbreaks) trends were observed. These dynamics indicate
a clear non-random spatiotemporal pattern of spread in specific
regions of the country, mainly concentrated in the Southeast and
Midwest regions, with some hotspots in the Northeast and North.
With this analysis, it was also possible to estimate the trend of
occurrence in the capitals of each Brazilian state (Figure 5). Natal
(Rio Grande do Norte) showed the highest trend of decreasing
4
outbreaks, whereas Goiânia (Goiás) reported a strong increasing
spatial trend of dengue outbreaks during the study period.
Figure 6 shows the spatial correlation between dengue out-
breaks and average temperature, daytime temperature varia-
tion, precipitation seasonality and population density; only the
last was not significant. Interpreting the LISA results, if a clus-
ter is high-high, there is evidence for neighbouring regions with
a high number of dengue fever cases. Clusters that are classi-
fied as low-low show neighbouring regions with a low number of
dengue fever cases. The bivariate local Moran analyses revealed
high-high and low-low spatial clusters based on temperature and
precipitation, and the Southeast and Midwest regions of the
country in particular presented coincident high-risk areas for
all variables, namely, high average temperature, high day-
time temperature variation and high precipitation seasonality
(Figure 7). These conditions make these areas most favourable
for the occurrence of epidemic outbreaks. Finally, we built a map
relating all significant variables to dengue outbreaks (Figure 8)
Transactions of the Royal Society of Tropical Medicine and Hygiene
Figure 4. Mann–Kendall analysis of dengue outbreaks in Brazil from 2000
to 2018. The positive trend is represented in red, whereas the negative
trend is represented in yellow.
and it was possible to observe a direct relationship between high
average temperature and high precipitation seasonality. How-
ever, the results of multiple regression among all variables (aver-
age temperature, daytime temperature variation, precipitation
seasonality and population density) and their interactions were
not significant (data not shown).
Discussion
Our findings indicate significant variation in the spatial distribu-
tion of dengue outbreaks in Brazil and it is possible to notice an
almost cyclical pattern, with intermittent periods of many munic-
ipalities with reported outbreaks over the study period (Figure 2).
During the period of study, the outbreak clusters were primar-
ily concentrated in the Northeast region, from where the trans-
mission of dengue fever extended throughout Brazil until 2018.
It is worth noting that dengue was reintroduced in Brazil in the
1980s (an outbreak in Roraima in 1981) after approximately 30 y
of absence.18 In Rio de Janeiro, DENV 1 was reintroduced in 1986
and DENV 2 in 1990, and from Rio it disseminated throughout the
country.19 Despite the dispersed spatial pattern of outbreaks, the
sustainability of dengue transmission is closely related to temper-
ature, as noted in other studies.20 Cities located below the trop-
ical zones presented a lower probability of outbreak occurrence,
with less favourable conditions for permanent transmission over
time, even in the presence of A. aegypti, as seen in the southern
municipalities.20 However, this may not be true for scenarios in
other countries such as Argentina. The temperate city of Córdoba
has been experiencing the emergence of dengue virus, transmit-
ted by the mosquito A. aegypti, since 2009, when autochthonous
transmission of the virus was first recorded in the city.21 Carbajo
et al.22 showed that temperature, although useful to estimate
annual transmission risk, does not fully describe the distribution
of dengue occurrence at the Argentina country scale.
The outbreaks comprised both expansion and retraction peri-
ods. Outbreak hotspots fluctuate along major circulation routes,
emerging mainly from large, urbanised and warm cities. Although
our Moran’s I analysis population density was not significantly
related to dengue outbreaks, population mobility may have an
important role in the spread of the dengue virus, as already
reported by other authors.20 Data from the IBGE17 showed that
the states of São Paulo, Rio de Janeiro and Goiás have the
largest number of immigrants, which could explain the emer-
gence of new outbreaks over the years. A similar process was
verified in Asia, where human mobility guided rapid epidemic
waves across countries.23 Nevertheless, under specific conditions
in our study (i.e. adverse climatic conditions, population immu-
nity or poor human mobility), epidemic waves finished and trans-
mission ceased. In this way, isolation may operate as a protec-
tive barrier for small municipalities. Isolated regions in northern
Brazil shown in Figure 3 (i.e. the Amazon region) remain protected
from large dengue outbreaks, most likely due to the high costs,
operational difficulties and long distances imposed on human
mobility.
The space-time fluctuations in the number of outbreaks in
the different regions are related not only to the significant flow
between populations from adjoining regions but also to the cir-
culating dengue serotypes and susceptible populations. DENV-2
and DENV-3 prevailed in most Brazilian regions in 2002–2006
and 2007–2009, respectively.24 DENV-1 re-emerged in 2009 in
the Southeast, being reported in about half of affected patients.
In 2010, DENV-4 resurfaced in the North, spreading to several
regions of the country.25 The increase in the number of dengue
outbreaks in Brazil in 2010 can be attributed to the re-emergence
of DENV-1 and DENV-4, together with the circulation of the
remaining serotypes. Thus, the spatiotemporal distribution of
dengue outbreaks reported here could be explained by these dif-
ferent circulating serotypes, which propagate more intensely in
the population within a specific period, as well as the immunity
level for each serotype.24 Estallo et al.7 showed that travel, migra-
tion and displacement within and outside the country becomes
a significant risk factor for dengue emergence.
In addition to control measures, the essential factor that leads
to the disappearance of an outbreak is gradual protection of the
population against the circulating dengue serotype. The speed
at which there is a decrease in incidence seems to be related
to the local transmission characteristics and the size of the ini-
tially susceptible population.25 The temporary interruption of out-
breaks observed in many Brazilian areas can be explained by the
interaction between the level of herd immunity and the rate of
dengue transmission in this specific population. Bennett et al.26
studied DENV-4 and revealed interesting patterns in the evolution
of dengue fever on the basis of its phylodynamics. The authors
showed that the reported epidemiological dynamics are depen-
dent upon the variation in diversity of viruses, including criti-
cal inter-epidemic reductions in genetic diversity consistent with
population bottlenecks that may greatly impact the DENV evolu-
tionary dynamics.26
The exploratory results presented here show that most warm
areas had a high probability of long-term outbreaks. We showed
that dengue has been expanding its transmission area across
5
T. S. de Azevedo et al.
Figure 5. Mann–Kendall spatial trend estimates for dengue outbreaks in each of the 27 Brazilian state capitals from 2000 to 2018. The blue bars
represent a decrease in dengue outbreaks, whereas the red bars represent an increase.
almost the entire Brazilian territory, consolidating as a hyper-
endemic disease along the east coast and the central regions.
These are essentially well-connected areas, and they play a
fundamental role in the maintenance and propagation of out-
breaks27 due to several combined factors such as propitious
mosquito reproduction (heat islands),28 human interactions,
enhanced virus dispersal, high levels of immigration and popu-
lation growth.20 It is known that the transmission of arboviruses
is more common in overpopulated regions,29 which is con-
sistent with the low incidence of dengue in most Amazon
areas. In Brazil, rapid and unplanned urbanisation results in
problems such as inadequate garbage disposal and poor san-
itary conditions. Estallo et al.30 highlighted the importance of
both local socioeconomic and demographic studies, as well as
the initiation of city cleaning campaigns, to reduce the avail-
ability of man-made containers in public places to decrease
mosquito infestation. Further, other studies have confirmed
that the high-risk areas for dengue are where the female
mosquito finds favourable conditions to feed and reproduce:
urbanised areas with high population density, with informal set-
tlements, and in places with unsatisfactory sanitation condi-
tions.24 These specific areas likely contribute most to the dis-
persion of arboviruses in metropolises. According to Rodrigues
et al.,24 ‘in recent decades, government policies aimed at the pre-
vention of arboviruses have been fragmented. In 1990, because
6
of the end of the Superintendence of Public Health Campaigns
(SUCAM) and the decentralization of monitoring actions for vector
outbreaks by surveillance officers, there was a partial break in the
continuity of actions. When dengue rates began to increase
again, some actions were resumed, although only occasionally,
to combat outbreaks or during the peak months of the epi-
demic. Another important factor was the failure of implemen-
tation of the sanitary network (water and sewage) throughout
the country. In 2007, the intended expansion of the sewage
system by the Growth Acceleration Program (PAC) to meet the
Millennium Development Goals did not occur as scheduled.’
These factors may have contributed to the dissemination of out-
breaks throughout the country. Additionally, this influences the
distribution of other diseases transmitted by A. aegypti, such as
Zika and Chikungunya.31
Dengue outbreaks are also related to environmental factors.
We observed that dengue outbreaks were fewer or absent in
areas with low temperatures (southern regions). It is known
that mosquito development and reproduction rates are impaired
at temperatures below 20°C and, consequently, the number of
dengue cases is reduced.32 Moreover, our study results suggest
that forested areas may be less susceptible to A. aegypti inva-
sions, which likely explains the low incidence of dengue in most
northern areas. Similar findings were reported by Nakhapakorn
and Tripathi,33 who revealed that urbanised areas have the
Transactions of the Royal Society of Tropical Medicine and Hygiene

Figure 6. Bivariate correlation between dengue outbreaks and (A) average temperature, (B) daytime temperature variation, (C) precipitation season-
ality and (D) population density for each Brazilian municipality (2000–2018). Moran’s I value represents spatial correlation between dengue outbreaks
with each variable; the p-value indicates its significance (p < 0.001). Confidence intervals for the Moran’s I statistics ranged from 0.9 to 0.99.

highest positive influence on dengue fever, whereas forest areas
have no influence. Carbajo et al.34 studied a municipality of
Argentina and showed that all autochthonous dengue cases
occurred in the urban environment with no sylvan cases. How-
ever, with increasing deforestation and subsequent urbanisation
of the Amazon region, the A. aegypti mosquito has found an
ideal spot for the reproduction and spread of the dengue virus in
non-immunised human populations. It is also worth noting the
sylvatic cycle of the dengue virus. In Brazil, the sylvatic vector
Haemogogus leucocelaenus was found to be infected with DENV-
1.35 In another study carried out in the Atlantic Forest of Bahia,
non-human primates were found with antibodies for DENV-1 and
2, and sloths (Bradypus torquatus) had antibodies for DENV-3.36
Therefore, despite not clearly being shown, it is possible that syl-
vatic cycles of DENV occur in Brazil, although more studies are
required to prove this hypothesis.37
In this study, we mapped the most probable areas for the
occurrence of outbreaks in Brazil (Figure 4), but this scenario may
change with the gradual increase in the average temperature.
Currently, the climate of most Brazilian regions provides a suitable
habitat for A. aegypti, which is widely dispersed throughout much
of the Brazilian territory. Aedes aegypti has been reported to be
present in 5172 of the 5494 municipalities in Brazil.38 Neverthe-
less, there are areas where, although the vector is present, there
is no outbreak of dengue. Higher temperatures may influence the
replication and survival of the virus, extrinsic incubation period of
a virus in the mosquito, susceptibility of the vector to viruses and
seasonality of virus transmission patterns,39 thus increasing out-
breaks in unexpected regions.
Our results must be considered in the context of a number
of assumptions and data limitations. First, because of high
demand and an inadequate number of health services and

7
T. S. de Azevedo et al.

Figure 7. Bivariate local Moran’s I of spatial association between dengue outbreaks and (A) average temperature, (B) daytime temperature variation
and (C) precipitation seasonality. The areas shaded in red (high-high) and blue (low-low) had a positive spatial correlation with dengue outbreaks.

Figure 8. Bubble chart and parallel coordinate plot showing multiple comparisons among three variables (average temperature, daytime temperature
variation and precipitation seasonality) with the number of dengue outbreaks in Brazil. The size of each bubble represents the number of outbreaks.
STD = Standard deviation. The maps were built with GeoDa software.

professionals, not all dengue cases are reported, especially dur-
ing major outbreaks. Second, we did not consider that mosquito
control measures could vary between different areas and munic-
ipalities or with time, and this may dramatically affect the prob-
ability of occurrence of dengue outbreaks. Similarly, the quality
of surveillance and clinical case detection may differ over time.
Further studies are needed to determine the key socioecological
factors (e.g. social, vegetation and mosquito density) that affect
the transmission patterns of dengue outbreaks. Stewart-Ibarra
and Lowe40 showed that local climate, vector densities and the
number of serotypes circulating influence interannual variabil-
ity in dengue fever transmission in southern coastal Ecuador,
highlighting the importance of considering both climate and non-
climate information in developing predictive models for dengue.
The current findings have shown that the transmission
cycles of dengue outbreaks vary in different spatiotemporal
scenarios and that the geographic distribution of the outbreaks
has decreased over time. During the study period, clusters of
outbreaks were primarily concentrated in the Northeast region
followed by the expansion of transmission of dengue fever in
Brazil until 2018. Our results indicate there is an enhanced risk
of dengue outbreaks when conditions of high average tempera-
tures and high daytime temperature variation are both satisfied,
which likely explains the low incidence of dengue in the southern
areas (milder temperatures). This is probably related to the life
cycle of the A. aegypti vector, which is extremely well-adapted
to the urban environment and requires high temperatures for
its reproduction. The Mann–Kendall analysis showed both pos-
itive and negative trends in Brazilian state capitals, and the
probability of occurrence of dengue outbreaks are mainly con-
centrated in Southeast and Midwest regions, with some hotspots
in Northeast, North and South regions. Although these maps
are preliminary and can be modified by socioeconomic and cli-
matic moving boundaries, the variations are not random. These

8
Transactions of the Royal Society of Tropical Medicine and Hygiene
findings suggest that further improvement in our understanding
of the impact of socioenvironmental change and ecosystem
stress upon the transmission of dengue fever and development
of control strategies is needed.
Supplementary data
Supplementary data are available at Transactions online.
Authors’ contributions: TSA, CL and FCN conceived the study. TSA car-
ried out data analysis. CL drafted the manuscript. TSA and FCN criti-
cally revised the manuscript for intellectual content. All authors read and
approved the final manuscript.
Acknowledgements: We especially thank the anonymous referees for
helpful suggestions that greatly improved this manuscript.
Funding: This work was supported by São Paulo Research Foundation
(FAPESP) [grant number 2017/10297–1].
Competing interests: None declared.
Ethical approval: Not required.
References
1 Gubler DJ. Epidemic dengue/dengue hemorrhagic fever as a pub-
lic health, social and economic problem in the 21st century. Trends
Microbiol. 2002;10:100–3.
2 Chowell G, Cazelles B, Broutin H et al. The influence of geographic and
climate factors on the timing of dengue epidemics in Perú, 1994-2008.
BMC Infect Dis. 2011;11:164–9.
3 Brady OJ, Gething PW, Bhatt S et al. Refining the global spatial limits
of dengue virus transmission by evidence-based consensus. PLoS Negl
Trop Dis. 2012;6:e1760.
4 Brazilian Ministry of Health. Available from: http://www.saude.gov.
br/saude-de-a-z/dengue/situacao-epidemiologica-dados [accessed
January 3, 2019].
5 Hu W, Clements A, Williams G et al. Spatial patterns and socioeco-
logical drivers of dengue fever transmission in Queensland, Australia.
Environ Health Perspect. 2010;120:260–6.
6 Estallo EL, Más G, Vergara-Cid C et al. Spatial patterns of high Aedes
aegypti oviposition activity in northwestern Argentina. PloS One.
2013;8(1):e54167.
7 Estallo EL, Carbajo AE, Grech MG et al. Spatio-temporal dynamics
of dengue 2009 outbreak in Córdoba City, Argentina. Acta Tropica.
2014;136:129–36.
8 SINAN. Sistema de Informação de Agravos de Notificação. Available
from: http://portalsinan.saude.gov.br/ [accessed October 10, 2018].
9 Azevedo TSD, Sallum MAM. The Use of Geographic information sys-
tems in the determination of areas at risk of dengue in the São Paulo
state. Geospat Health. 2017;42:23–9.
10 Fotheringham AS, Brunsdon C, Charlton M. Quantitative Geography:
Perspectives on Spatial Data Analysis. London, UK: Sage, 2000.
11 Brady OJ, Smith DL, Scott TW et al. Dengue disease outbreak defini-
tions are implicitly variable. Epidemics. 2015;11:92–102.
12 Mann HB. Nonparametric tests against trend. Econometrica.
1945;2:245–59.
13 Kendall M. Multivariate Analysis. London, UK: Charles Griffin &
Company, 1975.
14 Neeti N, Eastman JR. A contextual Mann Kendall approach for the
assessment of trend significance in image time series. Trans GIS.
2011;15:599–611.
15 Castillo KC, Körbl B, Stewart A et al. Application of spatial analysis to
the examination of dengue fever in Guayaquil, Ecuador. Procedia Env-
iron Sci. 2011;7:188–93.
16 Hijimans RJ, Camaron S, Parra J et al. Very high resolution interpolated
climate surfaces for global land areas. Int J Climatol. 2005;25:1965–
78.
17 IBGE. Instituto Brasileiro de Geografia e Estatística. Available from:
https://censo2010.ibge.gov.br/ [accessed May 12, 2019].
18 Osanai CH, Rosa APDAT, Tang AT et al. Surto de dengue em Boa Vista,
Roraima. Rev lnst Med Trop. 1983;25:53–4.
19 Nogueira RMR, Araújo JMGD, Schatzmayr HG. Dengue viruses in Brazil,
1986-2006. Rev Panam Salud Publica. 2007;22:358–63.
20 Barcellos C, Lowe R. Expansion of the dengue transmission area in
Brazil: the role of climate and cities. Trop Med Int Health. 2014;19:159–
68.
21 Robert MA, Tinunin DT, Benitez EM et al. Arbovirus emergence in the
temperate city of Córdoba, Argentina, 2009-2018. Sci Data. 2019;6:
1–6.
22 Carbajo AE, Cardo MV, Vezzani D. Is temperature the main cause of
dengue rise in non-endemic countries? The case of Argentina. Int J
Health Geogr. 2012;11:26–32.
23 Cummings DA, Irizarry RA, Huang NE et al. Travelling waves in
the occurrence of dengue haemorrhagic fever in Thailand. Nature.
2004;427:344–57.
24 Rodrigues NCP, Lino VTS, Daumas RP et al. Temporal and spa-
tial evolution of dengue incidence in Brazil, 2001-2012. PloS One.
2016;11:e0165945.
25 Anderson R, King AD, Innis BL. Correlation of E protein binding with cell
susceptibility to dengue 4 virus infection. J Gen Virol. 1992;73:2155–9.
26 Bennett SN, Drummond AJ, Kapan DD et al. Epidemic dynamics
revealed in dengue evolution. Mol Biol Evol. 2009;27:811–8.
27 Haggett P. The Geographical Structure of Epidemics. Oxford, UK:
Oxford University, 2000.
28 Azevedo TS, Bourke BP, Piovezan R et al. The influence of urban heat
islands and socioeconomic factors on the spatial distribution of Aedes
aegypti larval habitats. Geospat Health. 2018;13:1–8.
29 Ribeiro AF, Marques GR, Voltolini JC et al. Association between
dengue incidence and climatic factors. Revista de Saude Publica.
2006;40:671–6.
30 Estallo EL, Sangermano F, Grech M et al. Modelling the distribution of
the vector Aedes aegypti in a central Argentine city. Med Vet Entomol.
2018;32:451–61.
31 Aguiar BS, Lorenz C, Virginio F et al. Potential risks of Zika and
chikungunya outbreaks in Brazil: A modelling study. Int J Infect Dis.
2018;70:20–9.
32 Tun-Lin W, Burkot TR, Kay BH. Effects of temperature and larval
diet on development rates and survival of the dengue vector Aedes
aegypti in north Queensland, Australia. Med Vet Entomol. 2000;14:
31–7.
9
T. S. de Azevedo et al.
33 Nakhapakorn K, Tripathi NK. An information value-based analysis of
physical and climatic factors affecting dengue fever and dengue
haemorrhagic fever incidence. Int J Health Geogr. 2005;4:4–13.
34 Carbajo AE, Rubio A, Viani MJ et al. The largest dengue outbreak in
Argentina and spatial analyses of dengue cases in relation to a control
program in a district with sylvan and urban environments. Asian Pac J
Trop Med. 2018;11:227–30.
35 De Figueiredo ML, de C Gomes A, Amarilla AA et al. Mosquitoes infected
with dengue viruses in Brazil. Virol J. 2010;7:152–60.
36 Catenacci LS, Ferreira M, Martins LC et al. Surveillance of arboviruses
in primates and sloths in the Atlantic Forest, Bahia, Brazil. EcoHealth.
2018;15:777–91.
10
37 Figueiredo LTM. Human urban arboviruses can infect wild animals
and jump to sylvatic maintenance cycles in South America. Front Cell
Infect Microbiol. 2019;9:259–65.
38 Nunes MRT, Faria NR, Vasconcelos JM et al. Emergence and poten-
tial for spread of Chikungunya virus in Brazil. BMC Med. 2015;13:
91–102.
39 Epstein PR. Climate change and public health: emerging
infectious diseases. Encyclopedia of Energy. 2004;1:380–
92.
40 Stewart-Ibarra AM, Lowe R. Climate and non-climate drivers of
dengue epidemics in southern coastal Ecuador. Am J Trop Med Hyg.
2013;88:971–81.