Introduction: Dengue fever, a disease of serious epidemiological, social, and economic impact, has become a threat to global public health.

Objective: To determine the seroprevalence of dengue in five municipalities with hyperendemic and mesoendemic transmission.

Materials and methods: A cross-sectional descriptive study derived from a macro-project funded by the Ministry of Health and implemented by the Valle Department of Health. Using multistage probability sampling by cluster, 822 people were selected for the study.

Results: The seroprevalence of dengue was 91.36% using the IgG indirect ELISA test for dengue, and in addition, on applying the IgM capture test for dengue the seroprevalence was 21.41%. The joint seropositivity of IgM and IgG antibodies was 20.3%.

Conclusion: The high general seroprevalence of dengue from the IgG test shows the impact of this disease throughout the life history of the residents of these five municipalities. A high percentage of people with a recent infection had a history of dengue which favors the development of the severe form of the disease.

These results suggest the possibility of using the tetravalent vaccine given that where there are a greater number of antibodies there is a better immune system response to the vaccine.
 

• Dengue

• Seroepidemiologic Studies

• Colombia; Immunoglobulin G

• Immunoglobulin M

Pinzón Gómez EM, Carrillo MH, Lesmes Duque MC, Daza Rivera CF, Ortiz Carrillo ME, et al. (2016) Seroprevalence of Dengue in Five Municipalities of Valle del Cauca - Colombia. Clin Res Infect Dis 3(5): 1043.

WHO: World Health Organization; MASL: Meters above Sea Level; MSPS: Ministry of Health and Social Protection; VBD: Vector-Borne Diseases; PSU: Primary Sampling Unit; IgG: Immunoglobulin G; IgM: Immunoglobulin M; PRNT: Plaque Reduction Neutralization Test; SD: Standard Deviation; CI: Confidence Interval; Ab: Antibody; SIVIGILA: System of Surveillance in Public Health.

Dengue is a disease of serious epidemiological, social, and economic impact, which has become a growing problem and is a threat to global public health [1].

The region of the Americas has experienced a significant increase in the number of cases registered in the last 30 years, with indigenous transmission in almost every country [2-4]. In 2012, dengue was classified by the World Health Organization (WHO) as “the most important mosquito-borne viral disease in the world”, and in 2013, the largest incidence in history occurred with more than 2.3 million cases reported [5]. Dengue in Colombia constitutes a priority problem in public health due to many factors, including re-emergence with rising intensity of transmission, the increase in the frequency of outbreaks of severe dengue, simultaneous circulation of the different serotypes, the infestation by Aedes aegypti of more than 90% of the national territory located below 2,200 MASL, the introduction of Aedes albopictus, the urbanization of the population due to problems of violence and the behavior of epidemic cycles every two or three years, foremost among which is the epidemic of 1977 and those of 2002, 2007 and 2010. The latter is considered the largest registered in Colombia with more than 150,000 confirmed cases, 217 deaths and simultaneous circulation of the four serotypes [6,7].

In the year 2014, 110,473 total cases of dengue were notified to the Surveillance System in National Public Health (SIVIGILA), the national incidence for that year being 413.5 cases per 100,000 inhabitants. Valle del Cauca was the department with the second greatest number of reported cases in Colombia; however, its capital, Cali, presented the largest report per municipality at the national level [8].

As little is known of the real impact of the behavior of the transmission of the disease, the Ministry of Health and Social Protection (MSPS) of Colombia, proposed initiating a process of change in the way the Regional Directorates of Health and Districts confront dengue. They proposed the development of a dynamic and comprehensive model of sustainable intervention that would also be more cost effective. Consequently, a national macro-project has been developed to strengthen the technical operational response capacity of the program for Vector-Borne Diseases (VBD) to prevent and mitigate the effects of climate change in the municipalities presenting 70% of the cumulative loading of dengue in 21 departments of the country [9].

In the department of Valle del Cauca five municipalities were prioritized, according to hyperendemic and mesoendemic transmission of dengue, with the intention of evaluating the seroprevalence in these municipalities and broadening the epidemiological knowledge of the serological component, and thus obtain information to improve the development of regular and contingency programs to confront dengue based on health promotion policies, prevention and treatment of affected people.

A cross-sectional study was carried out from the secondary analysis of data obtained from the macro-project “Strengthening the technical and operational response capacity of the VBD program to prevent and mitigate the effects of climate change”, which was funded by the Ministry of Health and implemented by the Valle del Cauca Health Departmentduring 2014.

This study was conducted in five municipalities of Valle del Cauca prioritized epidemiologically for dengue (Cali, Palmira, Buga, Tuluá, and Cartago).

Study population and sampling design

The study population consisted of people who were habitual residents of the city blocks marked on regional maps, and who agreed to participate in the study. Rural populations were not included in the study.

The selection of participants was conducted on the basis of a multistage random cluster sampling, in which the primary sampling unit (PSU) was city blocks, followed by dwellings, homes, and finally, people. The sampling framework consisted of M= 18,163 city blocks. From the maps provided by the Planning Office of each municipality, stratification was as follows: Cali: 13,425, Palmira: 2,136, Buga: 990, Tuluá: 826, Cartago: 786. The blocks included in the study were selected randomly from the sampling frame of blocks in each municipality.

For the calculation of sample size, for each of the study areas, the following formula was used:

n=

N: Number people of the urban area of the 5 Municipalities

p: anticipated proportion of the prevalence of dengue.

p = 50%

q = 1 - p.

?: sampling error of 3.34%

1- α/2= 1.96 percentile corresponding to a significance of 5%

For the calculation of the sample size, an expected prevalence of 50% was assumed, together with a reliability of 95%, an estimation error of 3.34%, a percentage of non-response of 10%, and a design effect of approximately 2. The final sample was 880 people. The number of selected blocks per municipality was 30, according to the proposal of the World Health Organization (WHO) for the selection of samples for rapid assessment of coverage [10].

For the collection of information a survey was first developed and validated; the format included information of the dependent variables (history of dengue evaluated through IgG) and the presence of current dengue (IgM). Additionally, socio-demographic variables were investigated such as age, sex, and location (which were one of the criteria for eligibility for this study).

A standardized protocol was developed for taking and handling of laboratory samples endorsed by the Departmental Public Health Laboratory so as to guarantee the quality of the results.

From the dwellings included in the study, a member of the family was selected at random, and, after obtaining informed consent (or parental consent in the case of minors) a sample of around 10ml of blood was taken by venipuncture. The samples were centrifuged and separated after each session and were subsequently sent to the Departmental Public Health Laboratory to perform the Panbio Dengue IgM Capture ELISA test. The value of the cut-off point was 0.497 and the indexes were: negative, < 0.9; undetermined, 0.9 to 1.1; and positive, > 1.1. In addition, a dengue IgG indirect ELISA test was performed.

The seroprevalence of dengue was determined through detection in the blood of the dengue IgG antibodies, which are specific serotypes and induce immunological memory. To detect the dengue IgG antibodies, the indirect ELISA test was used which, according to the producer, has a sensitivity of 97.9% and specificity of 100%. At the same time, dengue IgM antibodies were identified using capture ELISA which has a sensitivity of 98.9% and specificity of 95.7%. The Plaque Reduction Neutralisation Test (PRNT) was not performed on patients with asymptomatic positive IgM.

This research was approved by the Scientific Technical Committee of the Valle Department of Health and complied with the national norms for research in human beings.

A total of 880 people were selected for the present study, 6.59% of which were not included due to no response (5.59%), samples not processed due to hemolysis (0.8%), and insufficient quantity of blood sample (0.2%), making the final sample 822 people. 65.8% were women. The average age of the participants was 45.8 years (SD=18.8), with a minimum age of 1 year and a maximum of 87; according to sex, the average age in women was 46.4 and 44.6 in men.

In relation to the dependent variable history of dengue from IgG, a prevalence of 91.4% (CI 95%: 89.4% - 93.4%) was found in the five locations. On stratifying the seroprevalence by municipalities it was found that it ranged from 89.3% to 95.4%, Cartago being the most affected municipality (95.5%), followed by Palmira (92.2%), Cali (91.2%), Buga (89.4%) and Tuluá (88.4%); however, these differences were not statistically significant. The sample was grouped by age and lifecycle finding a greater number of people between the ages of 15 to 44 years followed by the 45 to 59 year age group that corresponded to 41.6% and 28.8% respectively (Table 1)

Table 1: Seroprevalence of thehistory of dengue from IgG, according to sociodemographic variables, five localities of Valle del Cauca - 2014.

In relation to the other sociodemographic variables, 7.3% of those participating were Afro-Colombian,the occupation of 53.4% of respondents was the home, 54.6% had partners and 52.3% were of low socioeconomic status. No significant differences were found between categories in any of these variables (Table 1).

Statistically significant differences in seropositivity were found between age groups, for both IgG (p-value 0.033), and IgM (p-value 0.034). Additionally, significant differences were found in the seroprevalence of dengue by locality for IgM (p< 0.0001) with a greater prevalence of IgM antibody seropositivity found in the municipalities of Tuluá (50,9%), and Cali (24,4%), in comparison with the other cities (Table 2) (Figure 1).

Table 2: Current seroprevalence of dengue from IgM, according to sociodemographic variables, five localities of Valle del Cauca - 2014.

Figure 1: Seroprevalence of dengue from IgG and IgM, by localities, five localities of Valle del Cauca - 2014.

The joint seropositivity of antibodies (Ab) IgM and IgG in the population studied was 20.3%, therefore, it should be noted that 91.4% of persons with a recent history of dengue had already had the disease. For the locality variable, Palmira and Cali were the two municipalities that presented lower figures - 1.6% (IC95%: 0.3% - 3.7%) and 23% (IC95%: 18.8% - 27.3%) respectively. No statistically significant differences were observed in the other variables (Table 3).

Table 3: Joint seropositivity of IgM and IgG antibodies according to sociodemographic variables, five localities of Valle del Cauca - 2014.

Additionally, the seropositivity of joint antibodies (Ab) IgM and IgG according to age, shows a high percentage in the 5 to 14-year-olds in comparison with the other age ranges; however, there were no significant differences between them (Figure 2).

Figure 2: Joint seropositivity of IgM and IgG antibodies according to age. Valle del Cauca - 2014.

The present research was conducted in the department of Valle del Cauca, one of the localities that reported the highest number of cases of dengue in Colombia [8]. The results confirmed the intensity of dengue transmission in this department and the seroprevalence found in the municipalities studied demonstrated their classification as endemic sites [11-13].

Statistically significant differences were found in the seropositivity for dengue between localities (p <0.0001), with a higher prevalence of IgM antibody seropositivity in the municipalities of Tuluá (50.9%) and Cali (24.4%), compared with the other municipalities (Table 2), suggesting that different eco-epidemiologic conditions can impact the seroprevalence in different cities as found in this study (XX, YY, 15, 27). These conditions include: the policies and intervention plans for the prevention and control of vectors implemented over time autonomously by each city, the drainage systems, the population density of the city, population displacements, the history of transmission of the virus and the serotype transmitted, vectorial capacity, and the interactions between pathogen, host, and vector. Moreover, in a study conducted in two endemic localities in Colombia, it was found that these variables can influence the transmission of the virus within the models used. XX.

The seroprevalence of IgG antibodies found was 91.36%, and that of IgM antibodies was 21.41%. This finding was similar to that reported in other departments such as Quindío, Casanare, and Meta, which registered a seroprevalence of 92.5% [14]. Additionally, the results were similar to those found in another study conducted in five municipalities in Quindío with 658 subjects, residents of the urban area of the selected municipalities, where the average seroprevalence of IgG antibodies was 89.4% and that of IgM were 14.2% [15]. Nevertheless, in the year 1996 in the region of Urabá, Antioquia, a seroprevalence of 59.1% was found, which is lower than those found in the present study. These results show and confirm that each year there is an increase in the number of cases in the country since the year 2004 [16].

Studies carried out in other countries with environmental and sociodemographic characteristics similar to those of Colombia, have reported a high prevalence of antibodies to dengue virus, similar to that reported in the present study. In this regard, studies have been conducted in Mexico, Puerto Rico, and American Samoa. The seroprevalence of IgG antibodies in the municipality of Jáltipan (Mexico) for the year 2003, was 79.6% in the general population [17]. In 2006 in Puerto Rico, in 275 blood donors, the seroprevalence was 92% [18]. Finally, in the case of American Samoa, a seroprevalence of 95.6% was found in 794 persons between the ages of 18 and 87 years of age [19].

Although there were no significant differences between the female and male population in the five municipalities researched in the present study, these results are different to what was found in the study of American Samoa in 2010 where the seroprevalence in the female population was 94.9% [19], and to those found by Restrepo et al. 2004, in Urabá, Antioquia, where the seropositivity was higher in women (64.6%) compared to men [20].

It has been reported that dengue affects individuals of all age groups. In this study, specifically for IgM, significant differences were found in adults aged over 45 years with respect to the other age ranges. This is taking into account a period of prolonged exposure in older individuals.

The results of the study show a high seroprevalence of IgG and IgM in all municipalities, without finding differences according to socio-demographic variables such as sex, ethnicity, occupation and socioeconomic level. A simultaneous seropositivity of IgM and IgG was found in 20.3% of the population studied, with a higher prevalence in people between the ages of 5 and 14 years (figure 2). This could indicate a secondary infection by any of the serotypes of the virus, which represents an increase in the risk of complications in an upcoming event, particularly severe dengue.

Given this scenario the approach to combating this disease has focused on the use of methods that remove or avoid contact with the vector through the use of insecticides. These, in most cases, are applied inappropriately, generating a possible selection of mosquitoes resistant to the chemical agents used, [21] which can be evidenced indirectly through the high seroprevalence rates found in this study: 21.41% for IgM, 91.36% for IgG, and 20.3% for joint IgM and IgG? However, these results suggestthat it is possible to use another approach, for example, the use of the tetravalent vaccine which is currently being developed, as it has proved to be more effective in populations with a high seroprevalence and who have had multiple infections with the dengue virus [13,22]. Although the viral neutralization test (PRNT) was not performed it is reasonable to think that the majority of these seroprevalences are due to Dengue virus and not to another, such as the Zika virus which has a cross-reactivity with the ELISA test [23], since in the year in which this study was conducted the circulation of this last virus in the national territory had not yet been confirmed by laboratory by the National Institute of Health in Colombia [24].

Although the use of vaccines is an option that can be explored as a program of prevention and promotion, it is still in the study phase. There is, therefore, a clear need to intensify the development of integrated strategies for epidemiological surveillance, prevention, and control of dengue, which includes analysis of the multiple factors that are currently presented in the country and that can influence the behavior of the epidemiological disease, among them: the higher frequency of outbreaks of dengue due to the emergence of progressively shorter epidemic cycles, simultaneous circulation of the four serotypes of the dengue virus [25,26], the urbanization of the population of the country due to displacement [27], deficiencies in the coverage and quality of basic sanitation services, weaknesses in the operational capacity of the operational technical response of both regular and contingency prevention and control programs, the poor intersectoral and social participation [26], in addition to the effects produced on the vector by climate change [28].

There is also a need for the development of an inclusive and intersectoral policy that empowers all the actors involved in the epidemiological behavior of a disease, in addition to the use of molecular techniques to identify the pathogen in the sample and evaluate the potential serotypes associated.

The strengths of this study include the selection of the population through the sampling performed. Also, the validity of the tests used to determine the antibodies in the population, given that the sensitivity and specificity of both tests makes them suitable for population use. Weaknesses of the study include the non-performance of the neutralization test (PRNT) which is considered the gold standard for the detection and measurement of antibodies that can neutralize the viruses that cause various diseases. However, this type of samples is not done routinely in the surveillance system of the departmental public health laboratories as they do not have the operational capacity to do so.

Another weakness of the present study was that it was developed during working days and hours which generated unintentionally a selection bias, given that the female population tends to remain at home doing domestic chores while the male population is at work.

The results of the study show a high seroprevalence of IgG and IgM in the department of Valle del Cauca, with no statistically significant differences being found in the sociodemographic variables evaluated such as sex, ethnicity, occupation and socioeconomic level. The high general seroprevalence of dengue from the IgG test shows the impact of this disease throughout the life history of the residents of these five municipalities in the department of Valle del Cauca. A high percentage of those who had recent infection had a history of dengue, which favors the development of the severe form of the disease.

These results suggest the possibility of using a tetravalent vaccine which is currently under study as higher titers of antibodies have been found in people who have had multiple infections with viruses, therefore higher titers of antibodies suggest a better immune system response to the vaccine.

To officials of the Departmental Laboratory of Public Health, and to the Group of Environmental Health and Immediate Response Team of the Valle del Cauca Department of Health for the support in the undertaking of the project.

Disclosures

Results of this research were presented at the Second LatinAmerican Meeting of Public Health. September of 2016, Cali-Colombia.

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