Trans R Soc Trop Med Hyg 2020; 0: 1–11

doi:10.1093/trstmh/traa083 Advance Access publication 0 2020

Demographic and climatic factors associated with dengue prevalence

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ORIGINAL ARTICLE
in a hyperendemic zone in Mexico: an empirical approach
Francisco Espinoza-Gomez a,∗ , Oscar Alberto Newton-Sancheza , Arnulfo Hernan Nava-Zavala b,e
,
Maria G. Zavala-Cernab , Fabian Rojas-Lariosa , Ivan Delgado-Encisoa , Abril B. Martinez-Rizoc ,
and Felipe Lozano-Kastend

a
Facultad de Medicina, Universidad de Colima, Avenida Universidad 333, Colonia Las Viboras, Colima, Colima, Mexico 28040;
b
Facultad de Medicina Universidad Autonoma de Guadalajara; c Facultad de Medicina y Ciencias Quimicas de la Universidad
Autonoma de Nayarit; d Facultad de Medicina de la Universidad de Guadalajara; e Unidad de Investigación Biomédica,
Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Mexico
∗ Corresponding author: Tel: 1+52-312-61000, ext. 37501; E-mail: fespin@ucol.mx

Received 21 May 2020; revised 07 August 2020; editorial decision 11 August 2020; accepted 17 August 2020

Background: Many models for predicting dengue epidemics use incidence and short-term changes in climate
variables, however, studies in real-life scenarios for correlations of seroprevalence (SP) with long-term climate
variables and with integration of socio-economic factors are scarce. Our objective was to analyse the combined
correlation between socio-economic and climate variables with the SP of dengue in Mexico.
Methods: We performed a seroepidemiological ecological study on the Mexican Pacific coast. Dengue SP was
estimated by the presence of immunoglobulin G antibodies in 1278 inhabitants. We implemented multiple cor-
relations with socio-economic, climatic and topographic characteristics using logistic regression, generalized
linear models and non-linear regressions.
Results: Dengue SP was 58%. The age-adjusted correlation was positive with the male sex, while a negative
correlation was seen with socio-economic status (SES) and scholl level (SL). The annual temperature showed a
positive correlation, while the altitude was negative. It should be noted that these correlations showed a marked
‘S’ shape in the non-linear model, suggesting three clearly defined scenarios for dengue risk.
Conclusion: Low SES and SL showed an unexpected paradoxical protective effect. Altitude above sea level and
annual temperature are the main determinants for dengue in the long term. The identification of three clearly
delineated scenarios for transmission could improve the accuracy of predictive models.

Keywords: climate, correlation, dengue, seroprevalence, sociodemographic

Introduction of dengue.4,5 Consequently, there is considerable debate about

Dengue continues to be a severe threat to global public health,
as efforts to achieve its control have been very erratic and its inci-
dence continues to grow.1 It is a disease typical of tropical coun-
tries with hot climates and urban areas with poor public services.
Traditionally, researchers have associated dengue transmission
with demographic factors such as female gender, poverty,2 over-
crowding, low education, limited access to medical services and
inadequate urban sanitation.3 These assumptions are based on
the incidence of patients diagnosed with dengue. This strategy
can be very inaccurate because it does not take into account
the large proportion of asymptomatic infections and the low
sensitivity (11%) and specificity (79%) of the clinical diagnosis
the role of these sociodemographic factors as determinants of
dengue transmission.6 Therefore it is necessary to explore the
correlation of dengue transmission with sociodemographic vari-
ables over long periods in random samples at the individual and
community level. The estimate of seroprevalence (SP) or cumu-
lated incidence made in this way could also indicate the total
dengue burden, which is an indicator of epidemic risk at the
regional level.7
On the other hand, some researchers have implicated cli-
matic characteristics as risk factors for dengue epidemics. In this
sense, the ambient temperature, the altitude above sea level,
the amount of rain and the relative humidity are factors that

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1
F. Espinoza-Gomez et al.
have shown the most significant correlation with the incidence
of dengue.8 Ambient temperature is directly related to mosquito
survival, reproductive rate and vector capacity.9,10 In the case of
altitude, some authors have pointed out its effects on dengue
transmission as a secondary phenomenon due to temperature
changes, although they accept that altitude could be directly
related to the transmission of flaviviruses such as Zika virus.11
Based on these observations, scientists have developed stochas-
tic mathematical models to predict the places and times in
which dengue epidemics could occur. These models fundamen-
tally consider the incidence of dengue clinical cases as well as the
population density of the vector mosquito, mainly Aedes aegypti
(Linnaeus). They have established risk areas for dengue trans-
mission in human settlements, especially those located <500 m
above sea level with warm weather.10,12 In recent years there
have been warnings about the effect of global warming on the
spread of dengue transmission, although there is considerable
debate on the issue.13
According to this reasoning, places at low altitudes that
increase their average annual temperature could become
endemic for dengue, even if they are outside the tropical belt
and in developed countries such as southern Japan, China and
Australia.12 In contrast, high-altitude localities would continue to
be ‘protected’ despite their tropical climate. However, there have
been reports of A. aegypti infected with dengue virus at >2300 m
above sea level,14 as well as epidemic outbreaks of dengue at
1700 m above sea level.15 Therefore it is likely that eventual
temperature increases may increase the risk of dengue trans-
mission in the future, especially in cities at higher altitudes. This
interaction of temperature, altitude, rainfall and relative humid-
ity with long-term dengue transmission has barely been explored
and empirical evidence on the correlation of dengue transmis-
sion with climatic factors, particularly with altitude, is scarce.11,16
The analysis of the multiple interactions between climatic and
demographic variables with the SP of dengue could help us detect
persistent endemic areas where authorities should concentrate
on preventive actions. At the same time, such empirical explo-
rations could help in the construction of more accurate predictive
models.
The purpose of the present study was to estimate the
cumulative incidence of dengue in the long term by detecting
immunoglobulin G (IgG) antibodies against dengue in people liv-
ing on the western coast of Mexico. Another objective was to cor-
relate the SP of dengue over the years with sociodemographic
and climatic variables. The studied area has been repeatedly
attacked by dengue epidemics, with the circulation of several
serotypes, as has happened in other areas of Mexico.17
Materials and methods
Design and target population
We conducted an ecological cross-sectional analytical study in
rural and urban locations in the Mexican states of Jalisco, Nayarit
and Colima in western Mexico. The area comprises a total pop-
ulation of around 9 million inhabitants.18 The locations or geo-
graphic points mentioned are areas of approximately 1 ha with
an average of 500 people each and were distributed in an area
2
of approximately 112 040 km2 among 1200 communities in the
states mentioned above (see Figure 1). On a map of this region
taken from Google Earth, we chose 58 communities that were
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systematically located a distance of 10–15 km from each other
until we covered the entire region in question, excluding those
areas with communities of <200 inhabitants.
In contrast, given the high population density in the cities of
Guadalajara and Puerto Vallarta, in Jalisco, samples were taken
from two or three locations around those cities, trying to main-
tain the equidistance of approximately 10 km between them.
When it was not possible to obtain physical access to a specific
location, the team moved to the next closest community and
conducted the study there. In the centre of these locations we
registered coordinates using the Global Positioning System and
corroborated with Google Maps. Our team took samples from
1465 people; on average, 20 individuals in 10 randomly selected
houses in each locality. We conducted the study from April 2010
to December 2012.
Variables
The dependent variable was the SP, or cumulative incidence, of
dengue, estimated from the presence of anti-dengue IgG anti-
bodies in the serum of individuals from each locality. The SP was
defined as the rate of positive individuals/total sampled individ-
uals, or the Z score. The identification of IgG antibodies against
dengue was determined by an enzyme-linked immunosorbent
assay (ELISA). For this we obtained a blood sample (5 ml) by
antecubital venous puncture. After immediate centrifugation, the
serum was separated and transported at 4°C to the laboratory
and then stored at −70°C until the antibody test was performed.
The ELISA was performed following the manufacturer’s instruc-
tions (EI 266b-9601G, Euroimmun, Lübeck, Germany). This test
was performed blinded in duplicate and the Institute of Diagnosis
and Epidemiological Reference of the Ministry of Health of Mexico
validated the results.
Eligibility criteria
We included people between 2 and 90 y old with permanent res-
idence in the locality for at least 10 y (or their age in the case
of children) who agreed to collaborate with the study through
a written consent letter. We excluded subjects with chronic or
debilitating diseases, such as diabetes mellitus, cancer, tuber-
culosis or human immunodeficiency virus. The team obtained
a structured questionnaire from each participant that contained
questions about the following social and demographic variables:
age (in years), gender (female=0, male=1). To determine the
socio-economic status (SES) we used an ordinal scale with six cat-
egories: the lowest being the head of the family had primary or
no education, incomplete housing and without a car or Internet
connection and the highest being for high educational level, com-
plete housing with good finishes and significant–high expendi-
tures on education and health. This criterion follows the Mexican
Association of Marketing and Opinion Agencies.19 For the school
level we applied an ordinal scale, assuming the greatest risk for
those who did not have primary school or no education (2), an
intermediate risk for high school (1) and a low risk for people with
professional or postgraduate studies (0).
Transactions of the Royal Society of Tropical Medicine and Hygiene
Figure 1. Map of Mexico and the sampled area in the states of Nayarit, Jalisco and Colima during 2010.
Ecological variables
We registered the environmental conditions in each locality,
including the total population of the settlement, consulting the
website for Peoples of America20 and the Instituto Nacional de
Estadística y Geografía18 ; the marginalization index as an indi-
cator of SES by community, according to the Mexican govern-
ment21 ; the altitude above sea level or elevation (in meters); the
annual average relative humidity (in %), temperature (T, in °C)
and rainfall (pluvial precipitation, in mm) from 1990 to 2000. We
recorded these latter variables from historical data of meteoro-
logical stations belonging to the National Meteorological Service
closest to each locality.22 This proximity was calculated for carto-
graphic applications in arcminutes and corresponded to approxi-
mately 3 for the regional latitude (this is 4–5.8 km).
Statistical analysis
The sample size was calculated using the formula to estimate a
proportion, considering an average prevalence of dengue infec-
tion of 48% reported by previous surveys in Mexico,23 with a mar-
gin of error of 1%, obtaining a sample size of 1228 subjects that
were distributed proportionally in the 58 locations. For the analy-
sis of the correlation between the presence or absence of anti-
dengue IgG at the individual level, we used univariate logistic
regression, estimating odds ratios (ORs) and their respective 95%
confidence intervals (CIs). Next we used a multivariate uncondi-
tional model with the backward step method for the elimination
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of variables and the transformation of those polytomous or ordi-
nal variables into nominal dichotomous (‘dummy’) variables.
In the second level, to correlate the prevalence of dengue
by location with the environmental variables, we used a multi-
variate linear model and a subsequent non-linear adjustment.
For this curve fit we used the formula for non-linear symmetric
correlation:
a−d
y=d+  b .
1 + xc
For the multivariate analysis we used a general linear model24
and only p-values <0.01 were considered significant, accord-
ing to Bonferroni’s adjustment. The dependent variable (dengue
prevalence by locality) showed a distribution close to normality
(Kolmogorov–Smirnoff=0.167, p=0.068), so we used parametric
linear and non-linear correlation models.
Ethical aspects
Institutional boards of research and ethics at the Universidad
de Colima and the Secretaria de Salud del Estado de Colima
approved the protocol (#142/09). All the participants (parents or
legal guardians in the case of minors) signed a written informed
consent before application of the questionnaire or blood sam-
pling. After that, they all received their test results in confidence.
The work team delivered the database to the Ministry of Health
in each state following the procedures of the Mexican Institute of
Information (IFAI).
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F. Espinoza-Gomez et al.

Table 1. Dengue SP as determined by ELISA IgG and its association with demographic variables in 1278 individuals living on the western coast
of Mexico during 2012, using univariate, non-conditional logistic regression

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Variable N Positive OR 95% CI p-Value

Gender
Female (1) 911 508 0.73 0.57 to 0.94 0.014
Male (0) 367 232
Age (years)
≤10 31 17
11–20 183 99
21–30 242 139
31–40 266 145
41–50 204 110
51–60 155 94
61–70 132 90
71–80 50 34
≥81 (1) 15 12 1.009 1.003 to 1.05 0.0043a
Education level
Elementary or none (1) 924 518 0.75 0.6 to 0.97 0.03
Middle and superior (0) 354 222
SES
Low 556 286 0.62. 0.5 to 0.78 <0.001
Medium or highb 722 454

a For age, the reference group was ≥81 y against all others.
b For SES, the independent variable was expressed in a nominal scale taking the lower category (5 and 6) as the risk group.

Results mean dengue cumulated incidence in the 58 localities in the

Dengue SP
We analysed a total of 1278 valid samples, of which 740 were
positive for IgG, which represents a total crude SP of 58% (95%
CI 55.4 to 60.8). Of these, 906 were women and 372 men. The
main reason for the oversampling of women is because almost
the entire male population moves away from their communities
to work or go to school. The average age was 39.4 y; the edu-
cation level was primary or none 71.5%, medium 19.9%, higher
8.3%; and the SES was very low 133 (10.4%), low 424 (33.2%),
medium-low 419 (32.8%), medium-high 221 (17.3%) and high
80 (6.25%). Table 1 shows the correlation between dengue preva-
lence and demographic variables by location.
After the analysis with age-adjusted multivariate logistic
regression, only the education level showed an increase in its
OR from 0.75 to 0.9 (CI 0.94 to 1.06, p=0.045), while low SES
remained a paradoxical protective factor, independent of all oth-
ers (OR 0.62 [CI 0.47 to 0.89]). When we transformed the SES to
a dichotomous scale in which 0 was medium or high level and
1 was low or very low, the OR and the CI did not change. We
did not find interactions between any of the other demographic
variables.
Ecological correlations
With respect to the SP of dengue at each locality, Table 2 shows
the demographic and geographic characteristics as well as the
states of Jalisco, Colima and Nayarit.
Table 3 shows the correlation between demographic and cli-
matic variables with the SP of dengue at the macro level in
the 58 sampled communities. The demographic variables were
total population, the type of settlement (rural or urban) and the
marginalization index in each locality. The climatic variables were
the annual average temperature, the average difference between
the maximum and minimum temperature, rainfall and relative
humidity recorded during the last 10 y before sampling. We also
recorded the elevation above sea level in each locality.
The elevation above sea level showed the highest correlation
index (Pearson’s correlation 0.28, p=0.00001) and in the multiple
correlation model we found independence of this variable over
the others. The average annual temperature showed the sec-
ond most significant correlation with dengue; however, it seems
to depend on its correlation with altitude (R2 =0.73, p<0.00001).
Since the relative humidity and temperature have a high corre-
lation index between them (R2 =0.56, p<0.00001), we discarded
this variable from the last bivariate analysis. After the removal
of an ‘outsider’ case, a community located at 2120 m above sea
level with a dengue SP of 85% (Santa Teresa del Nayar, Nayarit,
key number: 4), the correlation between altitude and dengue
increased to R2 =0.32 (p<0.00001). In Figure 2 we show this cor-
relation using a non-linear symmetric model.
As can be seen in the Z-shaped curve, there are two quite dif-
ferent scenarios: first, a flat curve for locations below 1180 m
above sea level, and second, for communities between 1200

4
 Table 2. List of sampled localities with their demographic and geographic characteristics and dengue SP in the states of Jalisco, Colima and Nayarit during 2012

Annual Maximum − Sampled/

Elevation average minimum Pluvial IgG
Key Marginalization (meters above temperature temperature precipitation Relative positive,
numbera Locality name State Population index sea level) (°C) (°C) (mm) humidity n/n Prevalence
1 Novillero Nayarit 895 8.4 7 22.0 12.0 1200 94.4 20/18 0.90
2 El Resbalón Nayarit 704 8.5 35 25.6 15.5 1289 87.8 22/1 0.05
3 Tecuala Nayarit 13 212 5.7 14 25.6 16.0 964 87.8 20/20 1.00
4 Santa Teresa del Nayarit 1087 28.5 2122 21.0 18.0 754 64.0 19/16 0.84
Nayar
5 Palmar de Nayarit 1370 10.3 5 25.7 10.6 1030 81.7 20/15 0.75
Cuautla
6 Acatan de Piñas Nayarit 229 8.3 147 25.6 15.1 2058 80.5 20/19 0.95
7 El Venado Nayarit 1300 9.4 61 25.0 15.1 2057 75.3 20/16 0.80
8 Huajimic Nayarit 698 7.3 1132 20.6 20.0 928 72.4 20/19 0.95
9 Mecatán Nayarit 2523 7.9 312 22.8 15.0 1237 89.5 20/13 0.65
10 Benito Juárez Nayarit 332 863 10.0 550 20.3 13.5 1289 71.0 20/11 0.55
11 Santa Cruz Nayarit 1353 5.5 17 22.8 14.5 1237 86.3 20/13 0.65
Miramar
12 Las Varas Nayarit 12 403 6.2 28 25.7 14.0 1443 86.5 20/6 0.30
13 Cacalután Nayarit 390 8.2 908 24.5 15.7 945 67.6 20/18 0.90
14 Jala Nayarit 5143 5.1 1067 22.3 17.0 930 85.0 20/11 0.55
15 Aguamilpa Nayarit 646 24.5 95 27.4 13.0 1038 78.1 20/13 0.65
Transactions of the Royal Society of Tropical Medicine and Hygiene

16 Pitillal, Nuevo Nayarit 177 830 6.0 35 26.5 15.4 1591 78.6 12/12 1.00
Vallarta
17 San Sebastián del Jalisco 523 5.2 1400 19.0 16.0 1278 52.3 25/25 1.00
Oeste
18 San Marcos Jalisco 3101 5.0 1383 20.2 17.5 1038 58.3 25/23 0.92
19 Cuquío Jalisco 4122 5.5 1790 18.0 17.1 806 51.0 23/0 0.00
20 Yahualica Jalisco 14 265 5.1 1800 17.4 18.2 762 39.2 26/2 0.08
21 Mexticacán Jalisco 3516 6.1 1749 18.3 19.0 755 39.2 18/2 0.11
22 Lagos de Moreno Jalisco 92 716 4.5 1925 19.3 14.0 603 44.8 30/1 0.03
23 Unión de San Jalisco 6668 5.7 1923 18.2 17.6 672 44.3 20/2 0.10
Antonio
24 San Diego de Jalisco 4789 6.0 1947 18.6 17.3 624 44.2 25/3 0.12
Alejandria
25 Capilla de Jalisco 12 496 4.9 2060 18.3 17.0 869 44.3 26/0 0.00
Guadalupe
26 Puerto Jalisco 177 830 3.9 75 26.1 12.7 1073 78.6 13/11 0.85
Peñas–Puerto
Vallarta

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6
Table 2. Continued

Elevation Annual Maximum − Sampled/

(meters average minimum Pluvial IgG
Key Marginalization above temperature temperature precipitation Relative positive,
numbera Locality name State Population index sea level) (°C) (°C) (mm) humidity n/n Prevalence
27 Mascota Jalisco 8215 3.8 1267 20.7 14.8 1001 46.0 25/25 1.00
F. Espinoza-Gomez et al.

28 El Refugio Jalisco 5725 4.8 1303 20.5 18.5 883 60.0 25/25 1.00
29 Zapopan Jalisco 870 000 3.1 1594 20.6 15.5 1007 61.0 25/3 0.12
30 El Tuito Jalisco 2518 5.4 850 22.3 16.7 1563 90.0 21/8 0.38
31 Los Guerrero Jalisco 674 5.0 1297 21.2 17.7 908 56.0 25/23 0.92
32 Tlaquepaque Jalisco 542 000 4.3 1750 21.0 15.3 999 69.4 24/11 0.46
33 San Martín Zula Jalisco 2169 7.3 1537 20.2 15.8 843 68.0 25/25 1.00
34 El Josefino Jalisco 825 5.2 1597 19.6 17.8 858 60.5 25/25 1.00
35 Huascato Jalisco 1332 7.1 1617 20.2 16.8 791 58.3 24/23 0.96
36 El Molino Jalisco 1643 8.1 1570 20.5 18.8 773 70.1 25/25 1.00
37 Tenamaxtlan Jalisco 4706 5.0 1483 20.5 18.0 937 55.7 23/1 0.04
38 Atemajac d Jalisco 5014 8.8 2334 16.1 14.5 969 57.3 25/0 0.00
Brizuela
39 Zacoalco Jalisco 16 228 6.1 1363 21.3 14.7 404 50.1 26/8 0.31
40 Tomatlán Jalisco 7899 5.4 50 26.6 14.4 819 90.0 26/19 0.73
41 Ejutla Jalisco 1229 4.7 1495 23.3 15.0 856 68.0 25/1 0.04
42 La Manzanilla Jalisco 7751 4.9 2070 16.7 14.4 928 56.0 5/0 0.00
43 Concepción de Jalisco 4179 4.4 2135 16.3 14.5 948 68.3 21/1 0.05
Buenos A
44 Quitupan Jalisco 1520 6.0 1654 20.4 17.7 783 75.6 26/1 0.04
45 Cd Guzmán Jalisco 97 750 4.2 1536 19.8 17.3 537 59.7 19/0 0.00
46 La Rosa, Contla Jalisco 231 7.9 1179 22.8 17.6 1182 60.0 17/4 0.24
47 Punta Pérula Jalisco 530 5.4 8 25.1 12.8 790 90.0 21/16 0.76
48 Casimiro Jalisco 11 116 5.1 450 28.1 18.0 1658 88.4 24/17 0.71
Castillo
49 Tamazula Jalisco 17 741 4.4 1126 21.8 16.0 1037 61.4 25/9 0.36
50 Melaque Jalisco 6350 5.9 10 27.0 13.1 956 94.0 29/22 0.76
51 Minatitlan Colima 3961 5.2 754 22.9 17.3 1341 72.4 23/20 0.87
52 Miramar Colima 6783 3.9 38 25.7 13.3 994 75.0 21/21 1.00
53 Pueblo Juarez Colima 11 374 7.1 265 26.2 16.0 741 78.1 20/20 1.00
54 Pihuamo Jalisco 6300 6.6 738 24.8 17.0 1613 76.0 23/11 0.48
55 Cuyutlán Colima 926 6.5 9 27.0 14.0 798 86.0 26/25 0.96
56 Ixtlahuacán Colima 2484 6.1 170 27.1 15.1 692 77.8 24/23 0.96
57 El Naranjo Colima 233 5.6 403 26.1 18.0 672 76.0 19/17 0.89
58 Cerro de ortega Colima 5214 10.0 17 25.7 12.5 857 89.6 22/21 0.95
Mean 43 574 6.8 969.9 22.4 15.8 1010 69.4 1278/740 58 CI 57.9 to
58.1

a Keynumber: number assigned in map of Figure 4.

Elevation in meters above sea level
Mean temperature, mean variation of maximum–minimum temperature, pluvial precipitation and relative humidity are annual averages during 1999–2010 recorded at the
closest meteorological stations of the Servicio Meteorológico Nacional de México.

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Transactions of the Royal Society of Tropical Medicine and Hygiene

Table 3. Correlation between the demographic and climatologic variables with dengue SP (ratio of positive to total sampled people) in 58
localities of Jalisco, Nayarit and Colima during 2012 using a linear univariate and multivariate model

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Mean (95% CI)* Univariate Multivariate

Variable R2 p-Value R2 p-Value

Altitude (meters above sea level) 970 (474 to 1176) 0.28 <0.0001 0.04 0.14
Annual average temperature (°C) 22.4 (21.6 to 23.2) 0.273 <0.0001 0.014 0.39
Annual average of difference 15.83 (15.3 to 16.3) 0.006 0.37 0.005 0.63
between maximum and
minimum temperature (°C)
Pluvial precipitation annual 1010 (925 to 1095) 0.04 0.133 0.00002 1
average (mm)
Relative humidity (%) 69.44 (63.4 to 73.5) 0.18 0.0009 0.0041 0.64
Marginalization index 6.8 (5.8 to 7.8) 0.025 0.23 0.0053 0.6
Population18 43 574 (7574 to 79 574) 0.023 0.24 0.013 0.39
After backward stepwise deletion R2 p-Value
Altitude (in meters above sea 0.28 <0.00001
level)
Annual average temperature (°C) 0.022 0.28

Multiple regression coefficient R2 =0.322.

*Wald’s method for confidence intervals to 95%.

Figure 2. Correlation between SP of dengue (positive IgG/sample n) and elevation (meters above sea level) in the 58 locations studied on the western
coast of Mexico using a non-linear symmetric model.

and 1654 m above sea level, where we observe a very steep
slope in the curve; and then those places between 1700 and
2500 m above sea level, where we observe a new flattening. In
the first group (coastal places), the temperature showed a non-
significant correlation with the SP of dengue (R2 =0.09, p=0.39).
In the second group (medium–high), the correlation between
temperature and dengue showed an unexpected negative cor-
relation (R=−0.39, R2 =0.15), while in the high settlements, at
>1710 m above sea level, the correlation between temperature
and dengue increased to R2 =0.95 (p<0.00001). We obtained the
highest cumulated incidence at elevations <500 m above sea
level (SP 79%), a middle zone between 550 and 1650 m above
sea level (SP 61%) and a ‘protected’ zone at >1700 m above sea
level (SP <15%).
Regarding the non-linear correlation of annual average tem-
perature with dengue, we also found an S-shaped curve with a
significant correlation index and a ‘step-like’ contrast between
19.0 and 20°C, as can be appreciated in Figure 3. The SP of dengue

7
F. Espinoza-Gomez et al.
Figure 3. Correlation between SP of dengue and annual average temperature (°C) in the 58 locations studied on the western coast of Mexico using a
non-linear symmetric model.
at <19.8°C was of 19%, while at >20°C it increased to 69%
(t=4.89, p≤0.0001).
We outlined the geographical distribution of dengue cumu-
lated incidence by communities in the studied area according to
its altitude on a topographic map of Mexico available online.25 We
show this map in Figure 4. In this figure we see some commu-
nities of at >1600 m above sea level with a high SP of dengue.
These communities are settlements located relatively close to
the largest river basin in the area: Santiago, Lerma and Ameca
(key numbers of locations: 13, 15, 18, 28, 31–36), all with annual
temperatures >20°C.
Discussion
We obtained a global SP or cumulated incidence of dengue
of 58%, which is higher than that expected for Mexico.17 This
contrasts with values of incidence obtained from clinical cases
attended in the medical units, which tends to be significantly
lower.5 In the present study we looked for the probability of hav-
ing been infected with the dengue virus, not necessarily being sick
with dengue, over the last 10 y, so the obtained SP is very close
to the real endemicity of each locality.
Regarding the risk factors for the transmission of dengue at
the household level, we found a correlation with male sex. This
fact contrasts with other studies stating that the risk of dengue
infection is higher in women.26,27 We could explain this finding,
because most of those studies include patients attended in med-
ical units, which are usually women. According to our results, we
can assume that the male population could be more attacked but
not detected by the health system. The higher SP in the elderly is
not surprising since many studies reveal that this population has a
higher cumulative incidence of infections.27 Both at the individual
and community level, the lowest education level and SES showed
a paradoxical protective effect. This finding is in stark contrast to
8
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the traditional idea that dengue is a disease of poor and unedu-
cated people.2,28
Our current findings are similar to those previously reported
by our team in Colima,23,29 deepening the debate on the role
of poverty and illiteracy in the transmission of dengue.6,30 We
could attribute this phenomenon to the fact that subjects with
a higher SES and higher education tend to develop a kind of
self-confidence that leads to contempt for official preventive pro-
grams, while the lower SES stratum in Mexico probably more
faithfully follows such programs.
At the macro-environmental level, we did not find a significant
correlation of dengue SP with population size, the type of settle-
ment (rural or urban) or the marginalization index. Some authors,
like Braga et al. in Brasil,31 have implicated these variables as risk
factors for dengue transmission. An explanation for such discor-
dance could be that in their study, made in Recife, the authors
compared SES as whole neighbourhoods, while we used small
blocks of mixed SES. Another difference is that they included peo-
ple with higher SES who lived in apartment buildings with more
than one floor, while we only studied houses at ground level.
The climatic variables most significantly correlated with the
SP of dengue were the altitude above sea level and the average
annual temperature. Relative humidity showed a significant cor-
relation but depended on temperature, while rainfall was not cor-
related at all. When we analysed the correlations in a non-linear
way, we found a sharp sigmoid-shaped correlation of dengue
with altitude and with the average annual temperature. These
findings allowed us to assume a stratification of the communi-
ties for risk of dengue transmission as those located at <500 m
above sea level with average temperatures ≥20°C as highly risky
for hyperendemic transmission, those communities at >1700 m
above sea level with average temperatures <19°C as low risk and
those communities at 600–1690 m above sea level where the SP
seems to depend on other yet to be defined factors other than
temperature, altitude, rainfall, relative humidity or marginaliza-
tion index.
Transactions of the Royal Society of Tropical Medicine and Hygiene
Figure 4. Map of elevations above sea level (in meters) and prevalence of dengue in the 58 studied localities in Jalisco, Colima and Nayarit, Mexico.
Adapted from Topographic map.com. Topographic map of Mexico (2018). Available from: https://en-gb.topographic-map.com/maps/2qw7/Mexico/
(accessed December 2018).
Some of the places located at >1600 m above sea level and
with a high seroprevalence of dengue (map key numbers: 13,
15, 18, 28, 31–36) were settlements embedded in an isothermal
range of temperatures between 20 and 21°C along the largest
river basin in the zone (Ameca and Lerma-Santiago). This find-
ing could explain the displacement of dengue from the coasts
to the most central mountainous areas through hypothetical
‘thermal corridors’ along the banks of these rivers. Although the
primary way to get dengue is through human trafficking,26,32
it is feasible that some mosquito populations move through
warm airflows along large river basins, as Klassen and Hock-
ing33 pointed out for some sylvatic Aedes mosquitoes that move
through low altitude valleys in cold and higher altitudes. The rest
of the communities at >1700 m showed a SP <15%. These lat-
est findings indicate that even when the A. aegypti mosquito
can adapt to high altitudes such as 2000 m,16 Erase (Reyes
et al. 2002), the maintenance of endemic dengue transmission
is quite unlikely. A remarkable exception in our study was the
rural community of Santa Teresa del Nayar in Nayarit, located
at 2122 m, with a predominantly indigenous population (Cora)
and a very high index of marginalization, where we observed
a high prevalence of dengue infection. This specific finding
deserves a more in-depth study of the determinants for dengue
transmission.
Regarding the daily variation in temperature (minimum–
maximum), investigators such as Lambrechts et al.34 propose a
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relevant effect of this factor on the transmission of dengue virus
in vivo. In contrast, our findings in the field showed no relevant
correlation, either for extreme values or for their range of varia-
tion, at least in these long-term field findings. The mainstream of
studies of the risk factors for dengue transmission are mathemat-
ical stochastic models to estimate the perilous areas for eventual
epidemics. They are based mainly on climatic short-term changes
and in the temporal incidence of clinical dengue.28,35 The present
is one of the few empirical analytic analyses of dengue SP associ-
ated with demographic and climatologic factors made in a real-
life scenario.
The main limitation of this study is the relatively small area of
investigation, mainly caused by the presence of criminal groups
in many municipalities. The exploration of coastal areas with low
average temperatures could have yielded more relevant informa-
tion. For example, low-lying areas with temperatures <19°C (such
as many coastal areas in North America, Europe and Asia) may be
‘protected’ from dengue transmission because of their climatic
factors rather than their industrialization or development. This
situation could change in the coming years as a result of global
warming.12 Another limitation was the heterogeneity in the dis-
tance from the sampled places to the nearest weather station,
which ranged between 3 and 15 km. However, we believe that
this distance can be a reliable indicator of the isothermal con-
ditions surrounding communities. Finally, we did not determine
dengue serotypes by the plaque reduction test, since it would be
9
F. Espinoza-Gomez et al.
essential to delineate the behaviour of dengue virus serotypes in
different places.
Conclusions
The complex epidemiology of dengue and its risk factors have
contributed to the expansion of this disease throughout the world
despite multiple multinational initiatives to eradicate it. In the
coming decades, the implementation of dengue vaccine pro-
grams could change this story.36 For now, the primary strategy for
dengue control remains the application of preventive measures
focused on A. aegypti control in areas with a high risk of endemic
and epidemic transmission detected through predictive mathe-
matical models. Here we show an empirical experience on the
correlation of the SP of dengue with demographic and ecological
variables in a hyperendemic region of an endemic country such
as Mexico. Our data obtained in a real-life scenario can contribute
to perfecting the current predictive models of dengue dynamics.
The other relevant finding is that SES and poverty are not a factor
for the transmission of dengue, in line with recent reviews in this
regard.6
According to our results, the riskiest areas for dengue epi-
demics are human settlements located at low altitudes with
an average annual temperature >20°C, irrespective of their
educational or economic level. Therefore the health authorities
should reinforce preventive programs in these places even in
the absence of epidemics. In contrast, higher communities at
>1700 m above sea level with average temperatures <19°C
could remain relatively free of dengue, despite their low economic
development.
Authors’ contributions: FEG was responsible for the study idea, study
design, data analysis and drafting the manuscript. OAN was responsible
for the study idea and coordination of field work in Colima and Jalisco.
AHNZ was responsible for the study idea, coordination of field work in
Jalisco and laboratory studies. FRL was responsible for the coordination of
field work in Colima and Jalisco and laboratory studies. IDE was respon-
sible for laboratory studies, data collection and draft discussions. ABRM
was responsible for coordination of field work in Nayarit and laboratory
studies. FLK was responsible for coordination of field work in Jalisco and
draft discussions.
Acknowledgments: We thank our field work staff, which included stu-
dents, nurses and biochemists from the Universities of Colima, Guadala-
jara, Autonomous Guadalajara and Autonomous Nayarit and Dr Carmen
Guzman-Bracho from the Instituto de Diagnóstico y Referencia Epidemi-
ológica de la Secretaría de Salud, Mexico City, for validation of laboratory
tests and her advice.
Funding: The present project was financed by the Fondo Regional para
el Desarrollo de la Ciencia y Tecnologia del Consejo Nacional de Ciencia y
Tecnologia de Mexico (FORDECYT 2009-01: 117535).
Competing interests: None declared.
10
Ethical approval: The institutional boards of research and ethics at the
Universidad de Colima and the Secretaria de Salud del Estado de Colima
approved the protocol (#142/09).
Downloaded from https://academic.oup.com/trstmh/advance-article/doi/10.1093/trstmh/traa083/5903849 by Cornell University Library user on 13 September 2020
Data available: None.
References
1 Brady OJ, Hay SI. The global expansion of dengue: how Aedes aegypti
mosquitoes enabled the first pandemic arbovirus. Annu Rev Entomol.
2019;65:191–208.
2 Farinelli EC, Baquero OS, Stephan C, et al. Low socioeconomic con-
dition and the risk of dengue fever: a direct relationship. Acta Trop.
2018;180:47–57.
3 Swain S, Bhatt M, Biswal D, et al. Risk factors for dengue out-
breaks in Odisha, India: a case-control study. J Infect Public Health.
2020;13(4):625–31.
4 Martínez-Vega A, Díaz-Quijano R, Alexander F, et al. Dificultad para
el diagnóstico clínico temprano del dengue en un área endémica
y su impacto sobre el manejo médico inicial. Rev Med Chile.
2006;134(9):1153–60.
5 Messina JP, Brady OJ, Pigott DM, et al. A global compendium of human
dengue virus occurrence. Sci Data. 2014;1:140004.
6 Mulligan K, Dixon J, Chi-Ling JS, et al. Is dengue a disease of poverty?
A systematic review. Pathog Glob Health 2015;109(1):10–8.
7 Imai N, Dorigatti I, Cauchemez S, et al. Estimating dengue
transmission intensity from sero-prevalence surveys in mul-
tiple countries. PLoS Negl Trop Dis. 2015;9(4):e0003719.
doi:10.1371/journal.pntd.0003719
8 Fouque F, Reeder JC. Impact of past and on-going changes on climate
and weather on vector-borne diseases transmission: a look at the evi-
dence. Infect Dis Poverty. 2019;8(1):51–7.
9 Jetten T, Focks DA. Potential changes in the distribution of
dengue transmission under climate warming. Am J Trop Med
Hyg. 1997;57(3):285–97.
10 Capinha C, Rocha J, Sousa CA. Macroclimate determines the global
range limit of Aedes aegypti. Ecohealth. 2014;11(3):420–8.
11 Watts AG, Miniota J, Joseph HA, et al. Elevation as a proxy for
mosquito-borne Zika virus transmission in the Americas. PLoS One.
2017;12(5):e0178211.
12 Jung-Seok L, Farlow A. The threat of climate change to nondengue-
endemic countries: increasing risk of dengue transmission poten-
tial using climate and non-climate datasets. BMC Pub Health.
2019;19(1):934–8.
13 Barclay E. Is climate change affecting dengue in the Americas? Lancet.
2008;271(9617):973–4.
14 Ruiz-López F, González-Mazo A, Vélez-Mira A, et al. Presencia de Aedes
(Stegomyia) aegypti (Linnaeus, 1762) y su infección natural con el
virus del dengue en alturas no registradas para Colombia. Biomédica.
2016;36(2):303–8.
15 Herrera-Basto E, Prevots DR, Zarate ML, et al. First reported outbreak
of classical dengue fever at 1,700 meters above sea level in Guer-
rero State, Mexico, June 1988. Am J Trop Med Hyg. 1992;46(6):649–
53.
16 Lozano-Fuentes S, Hayden MH, Welsh-Rodriguez C, et al. The dengue
virus mosquito vector Aedes aegypti at high elevation in México. Am J
Trop Med Hyg. 2012;87(5):902–9.
Transactions of the Royal Society of Tropical Medicine and Hygiene
17 Amaya-Larios IY, Rojas-Russell M, López-Cervantes M, et al.
Seroprevalence of dengue in school children in Mexico ages
6–17 years, 2016. Trans R Soc Trop Med Hyg 2018;112(5):
223–9.
18 Instituto Nacional de Geografia e Informatica. Censo de población y
vivienda 2010. Available from: https://www.inegi.org.mx/programas/
ccpv/2010/default.html#Datos_abiertos.
19 Asociacion Mexicana de agencias de opinion y marketing. Criterios
para clasificar nivel socioeconómico en Mexico. Available from: https:
//nse.amai.org/data/.
20 PueblosAmerica.com. Pueblos de México. Available from: https://
mexico.pueblosamerica.com/.
21 Secretaria de Gobernacion, Gobierno de Mexico. Consejo
Nacional de Poblacion. Indice de marginación por localidad
2010. Available from: http://www.conapo.gob.mx/es/CONAPO/
Indice_de_Marginacion_por_Localidad_2010.
22 Servicio Meteorológico Nacional. Información climatológica por
estado 1981–2010. Gobierno de Mexico. Available from: https://smn.
conagua.gob.mx/es/informacion-climatologica-por-estado.
23 Espinoza-Gómez F, Hernández-Suárez CM, Rendón-Ramírez R, et al.
Transmisión interepidémica del dengue en la ciudad de Colima, Méx-
ico. Salud Pública Méx 2003;45(5):365–70.
24 Steel RGD, Torrie JH, Dickey DA. Principles and procedures of statistics.
A biomedical approach. 3rd ed. New York: McGraw-Hill; 1997, p. 322–
51.
25 OnlineMapFinder. Topographic map of Mexico. Mindspark Interactive
Network, 2019. Available from: https://es-mx.topographic-map.com/
maps/zn0c/M%C3%A9xico/.
26 Gomez-Dantés H, Farfán-Ale JA, Sarti E. Epidemiological trends
of dengue disease in Mexico (2000–2011): a systematic lit-
erature search and analysis. PLoS Negl Trop Dis. 2014;8(11):
e3158.
27 Pavía-Ruz N, Rojas DP, Salha V, et al. Seroprevalence of dengue anti-
bodies in three urban settings in Yucatan, Mexico. Am J Trop Med Hyg.
2018;98(4):1202–8.
Downloaded from https://academic.oup.com/trstmh/advance-article/doi/10.1093/trstmh/traa083/5903849 by Cornell University Library user on 13 September 2020
28 Sánchez-González G, Condé R, Noguez Moreno R, et al. Prediction of
dengue outbreaks in Mexico based on entomological, meteorological
and demographic data. PLoS One. 2018;13(8):e0196047.
29 Espinoza-Gomez F, de la Cruz-Ruiz M, Newton Sanchez OA, et al. Edu-
cation level and the risk of dengue infection and Aedes aegypti infes-
tation in an endemic area. Abstracts of the 6th European Congress
on Tropical Medicine and International Health and 1st Mediterranean
Conference on Migration and Travel Health. Trop Med Int Health.
2009;14:39.
30 Mondini A, Chiaravalloti-Neto F. Spatial correlation of incidence of
dengue with socioeconomic, demographic and environmental vari-
ables in a Brazilian city. Sci Total Environ. 2008;393(2–3):241–8.
31 Braga C, Luna CF, Martelli CM, et al. Seroprevalence and risk factors for
dengue infection in socio-economically distinct areas of Recife, Brazil.
Acta Trop. 2010;113(3):234–40.
32 Moreno-Banda GL, Riojas-Rodríguez H, Hurtado-Díaz M, et al. Effects
of climatic and social factors on dengue incidence in Mexican munici-
palities in the state of Veracruz. Salud Pública Méx. 2017;59(1):41–52.
33 Klassen W, Hocking B. The influence of a deep river valley system
on the dispersal of Aedes mosquitos. Bull Entomol Res. 1964;55
(Pt 2):289–304.
34 Lambrechts L, Paaijmans KP, Fansiri T, et al. Impact of daily tempera-
ture fluctuations on dengue virus transmission by Aedes aegypti. Proc
Natl Acad Sci USA. 2011;108(18):7460–5.
35 Morin CW, Comrie AC, Kacey E. Climate and dengue transmission: evi-
dence and implications. Env Health Perspect. 2013;121(11–12):1264–
72.
36 World Health Organization. Dengue vaccine: WHO position paper –
July 2016. Wkly Epidemiol Rec. 2016;91(30):349–64.
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