Title: Space and space-time distributions of dengue in a hyper-endemic urban space: The case of Girardot, Colombia

Transcription

1 Author's response to reviews Title: Space and space-time distributions of dengue in a hyper-endemic urban space: The case of Girardot, Colombia Authors: Mauricio FUENTES VALLEJO (mauricio.fuentes@fsfb.org.co) Version: 1 Date: 05 May 2017 Author s response to reviews: Responses to the comments of Reviewer #1 1. Figure 1 was missing Figure 1 was included (in Power Point format) and is currently in the inventory available in the editorial manager platform. In this submission it was included in PDF format. 2. Line , could the authors explain why the average number of reported dengue cases is higher in dry season? Would that indicate potential differential under-reporting over different periods? There is no apparent reason why under-reporting of cases could occur over different periods in Girardot. The following was added to clarify this point (line 1399): It is unlikely that this difference is due to under-report of cases in different periods. As stated earlier, there is an increase of tourism (grater presence of susceptible populations, higher population density) during the dry seasons that could have an effect on the increase of dengue cases. 3. Line 356, 'gradual movement' - does the author imply the two clusters were somehow linked? There is not enough evidence to state that these clusters are linked. The term gradual movement was changed by the term shifted, to avoid confusion (line 1490). Discretionary comments

2 4. Including socio-economic status in the maps will strengthen the argument on the association between dengue and poverty Unfortunately, no spatial information on socio-economic status is available for Girardot, so it is not possible to represent this information in the maps. Socio-economic information was assessed with extensive fieldwork. 5. Line 146, 23% of the reported dengue cases may be imported and there is a large number of tourists in June/July and Dec/Jan. It may also be informative to provide information of tourist hotspots in the map. Ongoing research is assessing urban centralities that could represent tourist hotspots, but is not available yet to enrich the maps of this current publication. Responses to the comments of Reviewer #2 This reviewer did not included comments Responses to the comments of Reviewer #3 1. The language in the manuscript needs extensive work to improve readability. At present, the language of the manuscript significantly detracts from clarity. Extensive language revision was made to the whole document and figures to improve clarity and readability of the manuscript (Nature Research Editing Services were hired). 2. The author does not define "highly endemic" despite using the term several times. This term was used two times: in the abstract and in the background sections. The term was initially used accordingly with a cited publication (Zambrano et al 2014). Nevertheless, the term was omitted in both sections, modifying the text as follows: Abstract (line 29): Dengue cases in the Americas have increased over the last few decades, affecting various urban spaces throughout these continents, including the tourism-oriented city of Girardot, Colombia.

3 Background (line 182): The Americas have reported an increase in cases over the past 30 years and local transmission has been reported over the entire region, excluding Canada, Uruguay, and Chile [3,4]. 3. The manuscript lacks a motivating reason why Giradot is interesting - is it a matter of it being a tourist heavy area? Is there something unusual about data availability? To address this comment, a paragraph was added al the end of the background section (line 547) to clarify this point: Girardot is a growing tourism-oriented city with an influence over surrounding municipalities including non-endemic cities such as Bogotá. Additionally, Girardot is situated in a hyperendemic region for dengue transmission. Although urban growth and tourism have been considered as important factors of dengue transmission elsewhere [4,19,26,27], insufficient evidence is available about these factors for Colombian cities. 4. Beyond the language issues, I found the discussion of the spatial and space-time analysis methods to be hard to follow and somewhat opaque Extensive revision of language helped to clarify the discussion of space and space-time analysis. Additional improvements, as detailed below, were made in this section in response to the comments concerning the discussion. In general terms the methods used to assess the distribution of dengue are complementary, and they allow to discuss different territorial dynamics that could explain the different distributions described in this study. 5. While two different methods for adjusting the spatial distribution of cases are discussed, there is little discussion of whether or not these methods agreed, or if only one was used in the analysis, the inclusion of the first method seems superfluous. Changes in the results and discussion sections where made to address this comment. The last paragraph of the results section was modified (line 1612): According to the synthesis (Map 4), dengue cases clustered in space and space-time described before showed different distributions. A persistent incidence of dengue (local Getis-Ord indices) was found in more consolidated urban areas, whereas the space-time clusters (Kulldorff s scan statistics) emerged towards the north and east of the city where urban expansion and a more dynamic urban space are present. Nevertheless, dengue clusters assessed with both methods were located outside of the central region of the city towards the periphery, corresponding to the neighbourhoods and residential areas with different characteristics and socioeconomic

4 conditions. The different distributions of space and space-time clusters could be related to different territorial dynamics as discussed in the next section. The discussion section was divided in three sub-sections to better show the specificities of each method and how they complement each other: - Space clustering of the incidence of dengue - Space-time clustering of the incidence of dengue - Dengue in Girardot: Among places of persistence and places of outbreaks the following changes were made. Also, the first paragraph of the discussion was modified (line 1622): This study combined spatial and spatio-temporal analyses, which have been proven useful [42] for assessing the distribution of the incidence of dengue in intra-urban settings. Although the observed clusters in Girardot shifted throughout time and space (Map 4), these patterns might be the result of different territorial dynamics related to urban functions, urban changes (i.e., urban expansion), demographic composition, or touristic activities. Further understanding of dengue persistence (space clusters) and outbreaks (space time clusters) in the context of hyper-endemic urban spaces could eventually help to guide prevention measures from a territorial perspective (i.e., where, when and how to intervene). Lastly, the last paragraph of the discussion section was also modified (line 2157): Complementary use of space and space-time analysis can reveal different underlying territorial dynamics. Structural or long-term urban conditions (e.g., deprived areas) might be related to persistent concentrations of dengue to a certain extent. By contrast, more unstable and temporal urban dynamics (urban expansion and the movement of people on different scales) might enhance spatio-temporal concentrations. This possible pattern would certainly need to be evaluated in the context of and particularities of specific urban spaces before arriving at generalized conclusions. 6. It is unclear, given the nature of the results, and the largely unstable distribution of dengue, how the author can argue that the results can be "valuable in decision making" seems puzzling - rather, they seem to indicate that advanced planning for case-clustering is essentially impossible beyond a few limited stable clusters. If the authors wish to assert this, an example of the kinds of decisions that could be informed by the results of this study. In the discussion section, the decision making affirmation was modified to state that with further research this could be fulfilled (line 1649):

5 Further understanding of dengue persistence (space clusters) and outbreaks (space time clusters) in the context of hyper-endemic urban spaces could eventually help to guide prevention measures from a territorial perspective (i.e., where, when and how to intervene). 7. While the author discusses the relatively large number of cases that take place in tourist areas, this likely warrants some greater discussion regarding the implications of this finding. To complement the discussion of space-time clusters and tourism, the following was included (line 2122): Findings concerning touristic economies and risk of outbreaks are sensible and have an important effect in local economies, as reported in the Indian Ocean during the chikungunya outbreak ( ) [48]. In the case of Girardot, recent outbreaks of chikungunya and Zika have concerned local authorities regarding health and economic impacts (mainly in tourism). 8. In the limitations, the author should note that they don't have strain type information. This could have profoundly different implications if the spatially stable clusters are of the same type vs. different types. In the line 641 it was added: In addition, the SIVIGILA database does not contain specific serotype infection information. Also in the study limitations section, the following phrase was added (line 2281): The absence of serotype information related to reported dengue cases limits the interpretation of the space and space-time clusters described in this study. 9. Figure 1 was not included in the PDF. The author should ensure that all figures are properly formatted. Figure 1 was included (in Power Point format) and is currently in the inventory available in the editorial manager platform. In this submission it was included in PDF format. 10. Figures 2 and 3 need substantially clearer labels on their axes. These figures were edited including axes labels. Figure 2: Dengue cases and Age group

6 Figure 3: Dengue cases, Precipitation (mm) and temperature ( C) and Date