The manuscript “Association of environmental factors and high HFMD occurrence in Thailand” is an interesting study investigating factors that differentiate day care centers (DCCs) with low and high HFMD occurrence in northern Thailand and factors associated with outbreak response capacity at those centers. The results indicate that high occurrence HFMD DCCs have fewer sinks in toilets and large DCC size in terms of number of children. In addition, high occurrence HFMD DCCs were less likely to have explicit plans for prevention and control of HFMD outbreaks. This study provides straightforward results regarding factors that may lead to worse HFMD outcomes and therefore could be very useful for behavioral or policy change in DCCs in northern Thailand. My major concerns are associated with clarity of the writing, specifically around the explanation of some methodology used and how those analyses support the results. I believe all the statistical methods are appropriate, but they are not well described and make it difficult to assess some of the results and conclusions.

Major concerns:

Methods: There is no explanation of what a content analysis is, how it was implemented in the study, and how that analysis supports the results presented. In the Methods, there is one sentence on line 132 indicating that a content analysis was used, which provides too little information to understand what this method is used for and how it was implemented by the authors. The results of this analysis are presumably very interesting (lines 166-195), but as the paper is currently written, it is unclear that these results come from the content analysis and what aspect of this analysis supports these results based on the data.

It is not clear to me why the authors conduct univariate analyses for each predictor variable of interest and then include all the predictor variables in a multivariate model. A multivariate analysis is sufficient, and better than univariate analyses, which do not account for other factors that may be important.

The authors never state the median numbers used to categorize DCCs as high or low HFMD case report areas (e.g., lines 87-89) and should do so either in the methods or results. Although this is somewhat minor, this distinction underlies the entire analysis and is important for contextualizing how these results compare to what is known more broadly in the field. Are the high and low categories reflective of high and low exposure areas more broadly in Thailand or elsewhere, or, are even low HFMD areas in this study still higher than many other areas (in Thailand or around the world)?

Writing: Overall, the manuscript could be written more clearly and concisely. Some phrasing is awkward forcing the reader to re-read sentences multiple times to understand the content. In addition, there are several typos throughout. I have pointed out some of these, but the authors should re-read closely for such errors. Other editing issues include topic sentences that do not cover the scope of the paragraph and paragraphs that only consist of one or two sentences.

Minor concerns: Background: This section could be improved by adding more context. For instance, a lot of information from lines 205-224 in the discussion would be better placed in the introduction to provide context for +certain factors were investigated in this study. There is also no mention in the background about management and response to HFMD outbreaks, which is a major component of the study.

The second paragraph of the introduction needs re-structuring and editing for clarity. For instance, the topic sentence does not cover the scope of the paragraph, temperature and rainfall are also climate factors, the phrase “improper environmental conditions” is not clear, and the sentence starting with “The conditions..” on line 62 does not stand alone sensibly.

It is not entirely clear to me why the third paragraph is relevant, other than the last sentence perhaps (lines 72-74).

Methods: Lines 85-86: This sentence does not make it clear whether the environmental and sanitation information was collected in this study and how this data was collected.

Line 90 & 115: what is a simple random method?

Lines 93-95: Why were 62 and 47 DCCs chosen? Am I understanding this sentence correctly that nine low and high HFMD DCCs were chosen for in depth interviews? Is 9 (18) an adequate sample size (e.g., did you do a power analysis)? Were analyses done separately for the 109 DCCs versus the 18 DCCs with in depth interviews?

Lines 96-97: Please rephrase for clarity, this sentence could easily be misread as individual questionnaires were developed and used by each DCC.

Lines 98-99: was this a systematic literature review? This sentence suggests a lot of work went into developing the questionnaire, but the details are so vague it is not clear if that is the case.

Lines 106-109: why are these questions listed whereas the questions in the other parts of the survey are not?

It would be helpful to include the questionnaire as a supplemental file so others could build on your work.

Line 110: What is IOC? Acronyms need to be written out the first time they are used.

The paragraph on lines 110-114 provide information that should be included in the beginning of paragraph that precedes it. The authors should consider combining these two paragraphs into one.

Line 121: was there actually an observational component to this study (“DCCs were observed…”)? If so, this needs to be explained.

Line 125: what does “double-entered” mean and why was this done?

There is a lot of extraneous information in the methods, for instance, (line 129) “the “Enter” mode was used to select the variable in the model”. At the same time, other methods could be better explained. Why were chi-square and logistic regressions chosen and what questions were they used to answer? Does the data meet the assumptions for these statistical tests?

Line 131: what does “quality of prediction of the outcomes in each step” mean?

Line 132: one sentence should not be a stand-alone paragraph, please combine with the previous paragraph.

Results:

Most of content between lines 136 and 147 can be removed as all this information is presented in Table 1.

Lines 157-163: Although it is reasonable to link a child’s risk of HFMD infection to attendance at a high HFMD DCC, the results should be presented more precisely in terms of the analysis (as was done in describing the univariate analyses results). Please rephrase the results of the multivariate logistic regression according to the actual analysis where the response was low or high HFMD DCC (rather than the chance of a child getting HFMD).

Line 148: Does the univariate analysis refer to a logistic regression where the response variable is a high or low HFMD DCC? This sentence makes it seem like the response variable is the number of HFMD cases per DCC.

Line 150: what do the authors mean by “high rates of having met the indoor light standard”? Shouldn’t each DCC fall into one of two categories here: meeting or not meeting the indoor light standard?

Line 167: “managements” should be “management” and “high-and” should be “high and”.

Lines 174-175 after semicolon: this is unclear. Do the authors mean that few DCCs overall had a plan and properly prepared chemicals regardless of whether the DCC was a high or low HFMD case report area?

Discussion: Density of children was not analyzed (this would be the number of children per unit area), please rephrase to total number of children throughout.

Lines 232: replace “in Method section” with “in the Methods section”.

Line 242: replace “then” with “than”.

Figures and Tables Fig. 1: why is China split and labeled by provinces whereas all other countries in the map are not?

It is confusing to have n represent two different samples sizes in the tables. Maybe use N for total sample size (62 or 47) and n for indicating sample size of specific categories/factors.

Table 1: • Typos: a) “Hiving a ill tribe child” should presumably be “Having a Hill tribe child”, although this could be a clearer (maybe “At least one Hill tribe child in DCC”)? b) “Proportion of a caregiver per children (persons)” should be something like “Ratio of caregiver to children” and then the labels should be 1:1-10, 1:11-20, and 1:20-Max. • Why were the breakdowns of size of DCC and ratio of caregiver to children chosen? Instead of using >80 children and >= 20 children, can you list the max number?

Table 2: • In the caption please indicate that OR stands for odds ratio and explain what ORadj means (i.e., how was the OR adjusted?). Also, why was an adjustment used for only two variables? • Compliance in the headings is confusing because it is within the parentheses, so it looks like it corresponds to the percent of n DCCs that are compliant. • What does (2) and (4) mean (e.g., (4) Large size of DCC under separate drinking glass)? • Typos or unclear phrasing: a) “Sufficient of toys for children” – remove of b) “cleaning utensils and toys/building” – I really do not know what this means c) “cleaning water glass” – not sure what this means either d) “han washing before meal” should be “hand”