A major finding of this study was that older individuals with confirmed dengue illness (symptoms/warning signs and lab confirmation) were more likely to be identified by AS in both 2014 and 2015 whereas children and adolescents with confirmed dengue illness were more likely to be reported via PS for both study years. While gender differences by surveillance system and/or dataset were not apparent in either year in any of the data sets, females made up a higher proportion of cases in all data sets in 2015. Also of interest was the observation that the proportions of adults with possible dengue reported to the MoH PS data system based on clinical symptoms only were more similar to the proportion of adults identified via AS and could represent similar clinical presentations and/or less severe disease.
The strengths of this study include the ability to compare a research-based AS system to an existing, mandatory PS system in an area with a high burden of arboviral illness. Since mandatory reporting of dengue fever has been required for some time in Ecuador, laboratory diagnostics were used to confirm dengue illness in a subset of more severe patients in the PS system. Overall, the methods for the collection of AS data were thorough, and included similar data to that collected routinely by the MoH. The cluster study design of the AS is relatively efficient compared to more intensive surveillance methods (e.g., cohorts), increasing the likelihood that this could become an operational AS approach for Ministries of Health with limited resources.
The observed demographic differences can be attributted to a combination of cultural factors, health seeking behaviors, the lack of clinical treatment options and differences in the clinical and immunological profiles of study subjects (8,9,19,29). Active surveillance is effective in detecting infections in individuals who are less likely to utilize standard clinical treatments (8,9,20,21,30). Alternative medicine and home remedy care is a popular cultural norm in Ecuador, often viewed as an equally effective treatment method for dengue by the general population (11). It is likely that many in the cohort of 20-64 year olds in this analysis did not seek clinical care because they were asymptomatic, had mild disease symptoms or were using alternative medicine to treat their symptoms. In addition, prior studies suggest that older males are generally less likely to seek clinical services than females (31); females, as the primary caregivers, are more likely to take themselves and their children to the doctor (29).
Other potential explanations for the demographic differences detected by surveillance system could include the lack of knowledge of disease dynamics and social inequalities such as limited education, income, and access to care as well as substandard housing and location within the city (5,7,10,16,32). Although many Machala residents do attend MoH health clinics for care, they may not recognize that other household members exposed to the same environment are also at a higher risk for infection, a phenomenon consistent with a lack of knowledge about dengue and its transmission dynamics. Urban/periurban location may contribute to the social inequalities seen in healthcare in areas with low socioeconomic status, substandard housing, and inadequate urban infrastructure (e.g., piped water, sewerage, garbage collection). Individuals living in periurban areas of the city are thought to be at increased risk for disease and may be among the cohort of cases not reported to the passive surveillance system, although a spatial analysis was beyond the scope of this study (5,7). These individuals may not have the ability or resources to take time off from work or to travel to receive clinical care.
Previous literature also has shown that the greatest burden of acute dengue infections occurs in children under 10, while the most severe manifestation of dengue is amongst adolescents aged 14 to 20 years who are likely experiencing a second infection(25,33,34). Results of our AS and PS comparison study support these observations. The highest frequency of confirmed dengue illness in both 2014 and 2015 occurred in those under 20 years of age reported via PS to the MoH. The adult dengue disease burden was more likely to be reported via AS (confirmed dengue illness), or in the the PS with clinical symptoms only (possible dengue) data set in this comparative analysis.
The youth (5-19 years) age range could also be classified as school aged children and adolescents, a cohort at risk of exposure to daytime mosquito bites around the home and school. Students are also in close proximity to one another, which allows for the mosquitos around the school to potentially spread dengue. Since “school” is the common denominator, school could potentially also be a focus for a strategic intervention for disease control. Many studies have concluded that comprehensive school interventions for prevention have been shown to be an effective strategy for dengue vector control (34–37). There is however, mixed evidence of the role of schools in propagating dengue virus transmission (38,39).
Overall in 2014, there was a higher incidence of laboratory confirmed dengue infection observed in Machala, Ecuador than in 2015. AS was successful in identifying a larger proportion of laboratory confirmed dengue cases in 2014 than was identified through PS reporting to the MoH, demonstrating the added benefit of conducting AS in a high disease burden area. Given the time frame of clinical illness, infections malaria, chikungunya and Zika were unlikely. The first cases of chikungunya were identified in Machala 2015 and the first cases of ZIKV in 2016; no autochthonous malaria cases were reported from 2012-2017 (40). It is likely that the outbreak of chikungunya superseded dengue infections in 2015. The emergence of chikungunya virus in Latin America was closely followed by the emergence of zika virus. Although there were no reported cases of zika in Machala at the time of this study, news of the WHO declaring zika a disease of global concern may have increased awareness and may have instilled a sense of fear which led residents to seek clinical care (41). The WHO declaration also led to increased financial resources and surveillance strategies for at risk regions.
It is possible that some of the “possible” dengue cases from the PS system were attributed to tick borne disease, as our recent study detected antibodies to spotted fever group rickettsial in 25% of individuals clinically diagnosed with dengue from Machala in 2014-2015 (42). However, it is likely that dengue was the primary vector-borne infection circulating in Machala in 2014.
During 2015, PS identified more laboratory confirmed cases of dengue illness than AS even though a majority of cases initially recorded in the PS dengue illness (with warning signs) data set were diagnosed with diseases other than dengue following lab confirmation. In 2015, a chikungunya epidemic emerged; an increased use of health clinics when symptoms appeared likely aided passive reporting overall that year. This behavior may reflect the severity of symptoms associated with chikungunya and a increased awareness of general mosquito-borne diseases in circulation in the region. Nonetheless, awareness of disease symptoms and outcomes by the public is key to influencing health seeking behaviors. Continuing education is a strategy that could help better inform and influence these behaviors resulting in more accurate PS case counts. For individuals who do not receive information or have restricted access to health care facilities, AS is an important safety net to capture additional cases and disrupt transmission.
Local climate likely also influenced observed dengue seasonality and peaks in transmission. Epidemiological curves provide information about peak transmission time and allow for the comparison of transmission dynamics and trends over several years. Our observed epidemiological curves during 2014 and 2015 were consistent with previous literature showing peaks in dengue transmission in this region at the end of the hot, rainy season (25). This timing is likely associated with the presence of open containers and reservoirs of standing water that accumulate during the rainy season, which are an ideal habitat for juvenile Ae. aegypti. The transmission of dengue begins when the mosquitos mature from egg to adult, and adult mosquitoes become infectious (able to transmit virus). In 2014, the dengue illness AS and PS peaks occurred around the same week while in 2015, the AS transmission peak occurred earlier than both PS transmission peaks. This suggests that, in some years, AS has the potential to identify cases earlier than the PS, thus informing public health officials of the need for proactive interventions. Other studies have found that complementary active surveillance methods such as syndromic surveillance or sentinel surveillance can lead to earlier detection of outbreaks (19,23).
Limitations
There are some limitations in our study, due in part to the observational nature of the design. Although clinical cases without laboratory confirmation were reported as part of PS (possible dengue cases), there was no equivalent category in the AS system. Nonetheless, we were able to compare the demographics of the possible dengue patient group to both the AS and PS dengue illness data sets, highlighting the similarities and differences. Even though index cases (symptomatic individuals who tested positive for dengue) in the AS study were initially indentified at one of the MoH sentinel clinics or the hospital, we were unable to identify with certainty those cases that also were reported to the MoH PS system. Consequently, we did not include the AS dengue illness cases in incidence calculations of the total burden of disease in the Machala study area. The reported incidence figures are therefore, underestimates of the true burden of laboratory confirmed dengue illness in the Machala area. However, AS study participants were provided results of NS1 rapid tests at time of enrollment. Finally, the incidence proportions reported were calculated based on the population of the Machala area, not the catchment area specific to the clinics or the country level population total. These incidence figures cannot be compared directly to incidence figures calculated either for the catchment area or the country because of the differing denominators employed.