The role of meteorological factors on mumps incidence among children in Guangzhou, Southern China.

Mumps, a common childhood disease, has a high incidence in Guangzhou city, China. It has been proven that mumps is influenced by seasonality. However, the role of meteorological factors among children is yet to be fully ascertained. This study explored the association between meteorological factors and the incidence of mumps among children in Guangzhou. Distributed lag nonlinear models were used to evaluate the correlation between meteorological factors and the incidence of mumps among children from 2014-2018. The nonlinear lag effects of some meteorological factors were detected. Mean temperature, atmospheric pressure, and relative humidity were positively correlated with mumps incidence, contrary to that of wind speed. Extreme effects of temperature, wind speed, atmospheric pressure, and relative humidity on the incidence of mumps among children in Guangzhou were evaluated in a subgroup analysis according to gender and age. Our preliminary results offered fundamental information to better understand the epidemic trends of mumps among children to develop an early warning system, and strengthen the intervention and prevention of mumps.

Introduction

Mumps is a common childhood disease caused by the mumps virus that mostly affects children aged 5–9 years [1, 2]. It manifests clinically as an inflammation of the parotid gland with precursory fever. Most cases are mild and self-limiting, but can result in some severe complications such as deafness, aseptic meningitis, and encephalitis [3]. The incubation period of mumps is 12–24 days, with a median of 19 days [4]. Mumps is not only transmitted by droplet spread, but also via direct contact or contaminated fomites [1].

Mumps can be effectively prevented by vaccination. A sharp reduction in incidence was observed after routine vaccination [5]; however, many countries, including France [6], Ireland [7], UK [8], and USA [9] have experienced resurgences of mumps and reported large scale outbreaks over the past decade. Since 2007, the mumps vaccine has been integrated into the National Immunization Program in China, and the measles, mumps, and rubella (MMR) or measles and mumps (MM) vaccine has been provided free of charge to children aged 18–24 months in Guangzhou since 2008 [10]. However, the incidence rates of mumps in China rose to 33.9/100,000 and 35.6/ 100,000 during 2011–2012 [11]; meanwhile, 10008 and 7856 mumps cases were reported in Guangzhou [10]. A one dose vaccine program is unavailable to fully control the epidemic of mumps, although the immunization coverage rate is about 80% to 90% nationwide [12]. The two doses vaccination program was recommended by the World Health Organization [13] and the polyvalent mumps vaccine was recommended in the USA [9]. Hence, mumps is still a serious public health concern among children not only in Guangzhou, China, but also worldwide.

The incidence of mumps showed apparent seasonality in various areas, with the peak in late spring, early summer, and winter. Different seasonal distributions were even observed in southern and northern China [11, 12]. This hinted that mumps incidence was influenced by seasonal undulation. Therefore, we hypothesized that meteorological factors might play a vital role in the spread of mumps. Recently, the effects of meteorological factors on some infectious diseases have been explored extensively as early warning signals of possible epidemics, such as those of hand, foot, and mouth disease [14], varicella [15], and influenza [16]. Limited studies have been conducted to explore the association between meteorological factors and the incidence of mumps. A study using the ARIMAX model in Beijing, China showed that increasing temperature would cause an increase in the incidence of mumps [17], whereas a study that used a generalized additive model in Jining showed that an increasing trend in the incidence of mumps was observed when the temperature rose above 4°C [18]. However, a study which applied Pearson’s correlation analysis in Czech Republic showed that there was no relationship between mumps incidence and drier and warmer weather [19]. Besides, a Poisson regression model was applied in a study on mumps in 10 cities in Guangxi Province [20]. However, most of the previous studies only focused on linear effects but not lag effects. A study conducted in Shenzhen city applied the distributed lag nonlinear model (DLNM) in exploring the relationship between wind velocity and mumps cases [21]. Studies conducted in Fujian Province and Guangzhou city applied the DLNM in exploring the nonlinear correlations between meteorological factors and the incidence of mumps [22, 23]. However, the nonlinear and lag effects of climatic factors on the transmission among children, who are the main population affected by mumps, are still unclear at present. A study conducted in Japan explored the linear relationship between meteorological factors and mumps incidence among children via negative binomial regression analysis [24]. What are the roles of meteorological factors on mumps incidence among children? There is an urgent need to explore these nonlinear relationships using lag effects.

In this study, an ecological methodology was used to analyze the features of mumps in Guangzhou from 2014 to 2018. We built DLNMs [25], which can flexibly depict the nonlinear correlation and describe delayed effects in time-series studies, to analyze the effects of meteorological factors on mumps transmission among children. The findings of our study may be helpful in developing an early warning system for mumps epidemics among children, improving preventative measures, and reducing the risk of mumps infection among children.

Materials and methods

Study region

Guangzhou is the third largest city in China with a total of 8.97 million registered inhabitants. It is a typical meteorologically humid subtropical area and is located within 112°57′E to 114°3′E and 22°26′N to 23°56′N (. In Guangzhou, the summer season is wet and hot, whereas the winter season is dry and cool.

Data sources

In this study, clinically diagnosed cases of mumps among persons younger than 18 years were obtained from the National Notifiable Disease Report System from January 2014 to December 2018. Clinically, mumps was defined as an acute onset of bilateral or unilateral tender, self-limited swelling of the parotid or other salivary glands lasting for more than 2 days. Mumps is a notifiable disease in Guangzhou; consequently, all clinicians are required to compulsorily report cases to local health authorities within 24 hours via the National Notifiable Disease Surveillance System.

Daily meteorological data, including mean temperature (°C), diurnal temperature range (°C) (highest temperature minus lowest temperature), atmospheric pressure (hPa), aggregate rainfall intensity (mm), wind speed (m/s), relative humidity (%), and sunshine duration (hours) were collected simultaneously from the Guangzhou Meteorological Bureau.

Statistical analysis

We performed a descriptive analysis of meteorological variables and the occurrence of mumps in Guangzhou. Based on scatter plots, we concluded that the correlations between the meteorological factors and mumps incidence were nonlinear. The Mann–Kendall and Pettitt tests were applied to initially analyze the tendency of the meteorological variables and mumps cases among children. Most of the variables tended to increase or decrease. Due to the reasons mentioned above, DLNMs were applied to detect the relationships between meteorological variables and the occurrence of mumps. Atmospheric pressure was strongly correlated with average temperature (r = -0.82, P<0.01) as per the Spearman’s correlation analysis. Hence, the two variables were not combined in a model to avoid the potential problem of collinearity. Poisson regression, performed with the quasi-Poisson function, was used to assess over-dispersion of daily cases of mumps in the DLNMs. The calculation is performed using the following equation: where Y represents the number of cases of mumps reported on day t; both α and δ are the intercepts; NS represents natural cubic spline; X represents meteorological variables, such as temperature, diurnal temperature range, rainfall, atmospheric pressure, wind speed, relative humidity, and sunshine hours; df is the degrees of freedom; Holiday is defined as a binary variable (if day t is a public holiday or school vacation, it is marked as 1, otherwise it is marked as 0); Dow represents the day of week effect; and Time denotes long term trends and seasonality. We selected the df of day to control long term trends, seasonality, and meteorological variables using the Akaike information criterion (AIC). Based on the AICs, we chose df = 3 for NS according to the meteorological variables mentioned above. After combining the incubation period of mumps, df = 24 was chosen for mean temperature, atmospheric pressure, and wind speed, and df = 14 was chosen for relative humidity.

Extreme high effects were defined as when the value of meteorological variables were beyond the 97.5th percentile; when the value was below the 2.5th percentile, it was defined as an extreme low effect.

All statistical tests were two-sided. Analysis items with P<0.05 were considered statistically significant. All statistical analyses were performed using R version 3.5.3 (The R Development Core Team, Vienna, Austria) and the DLNMs were built using the dlnm package in the R environment [25].

We performed the sensitivity analyses by shifting the df (5–9) per year to control for seasonality and long-term trends using time, and changing the df (4–7) for mean temperature, atmospheric pressure, diurnal temperature range, wind speed, accumulated rainfall, relative humidity, and sunshine hours.

Ethical considerations

The study protocol was approved by the Ethics Committee of the Guangzhou Center for Disease Control and Prevention. All data were fully anonymized before we accessed them.

Results

From January 1st, 2014 to December 31st, 2018, a total of 9842 mumps cases among persons younger than 18 years were reported in Guangzhou. During 2014 to 2018, the breakdown of mumps cases was 1962, 2077, 1838, 1977, and 1988, respectively. The gender ratio was 1.83 (6362 males to 3480 females). Among the groups aged 0–3, 4–6, 7–14, and 15–17 years, there were 2197 (22.32%), 3773 (38.34%), 3672 (37.31%), and 200 (2.03%) cases, respectively. The peak of mumps occurrence in the study period occurred from May to July, with a total of 3087 cases (31.37%) (.

A description of meteorological variables and mumps cases is given as follows (. The mean daily temperature was 22.24°C, and the means of diurnal temperature, aggregate rainfall, atmospheric pressure, wind speed, relative humidity, and hours of sunshine were 8.20°C, 6.04 mm, 1005.41 hPa, 2.16 m/s, 79.19%, and 4.42 hours, respectively. The monthly distribution is shown in the monthly boxplot of meteorological factors (. The results of the Mann–Kendall and Pettitt tests are shown in . The variables of DTR, rain, pressure, wind, relative humidity were statistically significant. Wind and relative humidity had a rising tendency, whereas the DTR, rain and pressure had a decrease tendency. No tendency was observed among the variables of cases, temperature and sunshine hours.

shows the interaction network between meteorological factors and mumps cases among children, the strongest interaction was observed between temperature and mumps cases. Temperature, sunshine hour, relative correlation and aggregate rainfall had a positive interaction with mumps cases, whereas atmosphere pressure, wind speed and DTR had a negative interaction with mumps cases. Spearman’s correlation analyses revealed that the incidence of mumps was positively correlated with mean temperature, relative humidity, aggregate rainfall, and hours of sunshine. On the contrary, wind speed and atmospheric pressure were negatively correlated with the incidence of mumps. Mean temperature was strongly correlated with atmospheric pressure (r = -0.82, P<0.01).

The interaction network between meteorological factors and mumps cases among children in Guangzhou, 2014–2018.

*cas represents cases; tm represents temperature; prs represents atmospheric pressure; wnd represents wind; dtr represents diurnal temperature range; ran represents rain; rhm represents relative humidity; sun represents sunshine hours. The green line means positive relationship, whereas the red one means negative relationship. The width of the lines dedicates the degree of r. The thicker is the line, the greater is the interaction.

illustrates the correlation between mumps cases and meteorological variables with different lag periods in Guangzhou. Specific features were observed in various variables with a nonlinear curve. The highest relative risk (RR) was 1.005 (95% confidence interval [CI]: 1.001–1.010) at lag day 21, when the daily mean temperature was 25.0°C. When atmospheric pressure was 1027 hPa at lag day 0, the lowest RR was 0.775 (95% CI: 0.655–0.916). When relative humidity was 72.0%, the highest RR was 1.014 (95% CI: 1.003–1.026) at lag day 12. When wind velocity was 8.70 m/s, the highest RR was 1.269 (95% CI: 1.033–1.560) at lag day 11.

For a better explanation, the one-dimensional curves were plotted about the overall effects of meteorological factors over the corresponding lag days (. In a word, mean temperature, atmospheric pressure, and relative humidity were associated with mumps incidence, unlike wind speed. The RR of mean temperature significantly increased from 10°C to 23.6°C, whereas that of wind speed significantly declined from 1.9 to 4.5 m/s. Atmospheric pressure and relative humidity both showed a reverse U-shaped curve relationship with mumps. However, the RRs just had a significantly increasing trend before the atmosphere pressure as 992 hPa and the relative humidity as 60%, respectively. There were no significant relationships between other meteorological variables and the incidence of mumps in our study.

The estimated overall effects of mean temperature, diurnal temperature range, atmospheric pressure, wind speed, relative humidity, and sunshine hours along corresponding lag days.

The Y lab represents the value of relative risk, the X lab represents the value of relevant variables. The red lines represent mean relative risks and the grey regions represent 95% CIs.The black vertical line represents the medians of the climatic factors, and the dotted lines represent the 2.5 percentile and the 97.5 percentile for the meteorological factors, respectively.

The cumulative extreme effects of meteorological factors on mumps along the corresponding lag days are shown in . As shown in , the extreme low effect of temperature was significant and the lowest RR was 0.88 (95% CI: 0.83–0.93) at lag day 0, whereas the extreme high effect of temperature was not significant. On the contrary, the extreme high effects of atmospheric pressure and wind speed were statistically significant, whereas the extreme low effects were not. For atmospheric pressure, the lowest RR was 0.88 (95% CI: 0.82–0.94) at lag day 0. For wind speed, the lowest RR was 0.94 (95% CI: 0.89–0.98) at lag day 0. Regarding relative humidity, the RR of the extreme high effect was 0.96 (95% CI: 0.94–0.99) at lag day 2, and the RR of the extreme low effect was 0.96 (95% CI: 0.93–0.99) at lag day 2. For the extreme high and low effects of sunshine hours, the RRs were 1.03 (95% CI: 1.02–1.04) at lag day 2 and 1.02 (95% CI: 1.01–1.03) at lag day 17, respectively.

The extreme effects of mean temperature, diurnal temperature range, atmospheric pressure, wind speed, relative humidity, and sunshine hours with extreme high effects (97.5%) and extreme low effects (2.5%).

The Y lab represents the value of relative risk, the X lab represents the value of lag day. The red lines represent mean relative risks and grey regions represent 95%CIs.

In the analyses by subpopulation, the extreme low effects of temperature, atmospheric pressure, and relative humidity, and the extreme high effect of wind speed were statistically significant in the female population, but no significant extreme effect was observed in the male population. The extreme low effect of temperature was observed in the 4–6 year old group (RR = 0.25, 95% CI: 0.11–0.60) and 15–17 year old group (RR = 0.01, 95% CI: 0.00–0.57). The extreme high effect of atmospheric pressure was observed in the 4–6 year age group (RR = 0.46, 95% CI: 0.21–0.98) (.

Sensitivity analyses indicated similar results after the changes in the df for long-term trends and seasonality. Altering the dfs for temperature, atmospheric pressure, wind speed, and relative humidity, the original models showed better robustness compared to their alternatives.

Discussion

In this study, the incidence of mumps among children in Guangzhou fluctuated seasonally with the epidemic peak from May to July. The trough of mumps incidence among children occurred in February, coinciding with the winter holiday in school. However, our result differed from that of a study conducted in Ireland, which detected a relatively low mumps incidence in summer and a peak in autumn [7], and a study conducted in the Netherlands with two seasonality peaks in spring and autumn [26]. In China, the epidemic pattern in Guanghzou also differed from that of Beijing city, Zibo city in Shandong province, and Chongqing city, which showed two epidemic peaks from April to July and October to January, with an emphasis on the former [17, 27, 28]. It indicated that the effect of meteorological factors on the occurrence of mumps may be distinct in various regions with particular climatic features.

Climatic variables such as temperature, relative humidity, and wind speed have been proven to play a key role in the occurrence of certain infectious diseases [29-31]. Recently, more and more attention has been drawn to the effects of meteorological factors on mumps incidence. Some studies have been conducted to explore the relationships between meteorological factors and mumps cases; however, most of the studies just detected linear relationships without lag effects. Recently, DLNMs have been applied widely to evaluate these nonlinear correlations with lag effects [10, 21, 23]. However, these relationships among children still need to be explored.

To the best of our knowledge, this is the first study to apply DLNMs to detect the effects of meteorological variables on mumps incidence among children in a subtropical city in China. Nonlinear relationships were observed in some meteorological variables in our study. When the mean temperature ranged from 10–23.6°C, the RR showed an increased trend. Our finding was not fully consistent with previous studies. A study conducted in Mexico showed that the mumps incidence declined markedly during the summer [32]. However, a study conducted in Taiwan [33] reported that the incidence of mumps started to increase at a temperature of 20°C, and started to decline after 25°C, whereas a study conducted in Jining, China [18] and a study focused on children in Japan [24] both reported linearly positive associations between mumps incidence and temperature. A previous study conducted in Guangzhou [22] also revealed a positive correlation between mean temperature and the incidence of mumps in the overall population. However, another study conducted in Jining showed a U-shaped relationship curve between mean temperature and mumps incidence [34]. The discrepancy may be due to the differences in methodology, geographic location, and climatic characteristics. The incidence of mumps depended on the contact rate, which might be influenced by social behavior [35]. A previous epidemiologic study conducted in Canada showed that adolescents usually engage in more physical activity in the warmer months than in the colder months [36]. Children are more likely to come into contact with each other in warmer weather, which might result in an increase in the incidence of mumps. When the temperature continued to increase, outdoor activities among children might decrease, reducing the risk of mumps infection; however, the extreme high effect was not statistically significant. For the same reason, the risk of mumps infection will be reduced in extreme cold conditions; however, the accumulated extreme cold effect was only observed significantly among females. These might explain our finding among children in Guangzhou and shows that preventative measures and health education should be strengthened in the temperature range mentioned above in our study.

The results of some studies were inconsistent with ours. For example, relative humidity was found to have a negative impact on mumps incidence with a threshold of 54% in Jining, China [18]. However, another study conducted in Jining showed that the effect of relative humidity on mumps increased slightly and then decreased quickly, with a threshold of 64% [34]. Besides, a study conducted in Taiwan [33] found no correlation between relative humidity and mumps incidence. Our study showed a U-shaped relationship between relative humidity and mumps incidence among children in Guangzhou, with a statistically significant increase before a relative humidity of 60%. Meanwhile, nonlinear extreme high and low effects of relative humidity on mumps incidence were both found among children. Studies on the mechanism underlying the effect of relative humidity on mumps incidence are rare and should be carried out in the future. One possible mechanism might be as follows. Droplet spread is one of the modes of transmission of the mumps virus [1]. When the relative humidity is low, water in the droplets evaporates quickly. The longer the droplet with mumps viruses remains airborne, the easier it is the mumps infect the children [37]. As the relative humidity increases, the effects become insignificant. However, an extremely high effect of relative humidity was observed with an RR of 0.96 (95% CI: 0.93–0.99) at lag day 2, which may be explained by the fact that high relative humidity often coincides with heavy rain, which will make children more likely to stay at home [38] and reduce the contact rate. More studies should be carried out to identify biological evidence.

Wind could affect the suspension time of viruses and their diffusion distance [39, 40]. Our study revealed that the RR decreased as the wind speed surpassed 1.9 m/s till 4.9 m/s. Moreover, the high effect of wind speed yielded an RR of 0.94 (95% CI: 0.89–0.98). Our study result was similar to that of a study conducted in Shenzhen, which depicted a reverse V-shaped relationship between wind velocity and mumps incidence, with the peak at 2 m/s [21], and a study conducted in Fujian province [23], which showed a negative relationship between wind speed and mumps incidence. In view of the resuspension phenomenon, the concentration of local viruses may be diluted by higher wind velocity [39, 41], which could possibly explain our finding. In the subpopulation analysis, an accumulated high effect of wind speed was observed among females. This may be explained by the reduction in outdoor activity among females in the extreme high wind velocity weather. Based on our findings, regular ventilation might be helpful in protecting children against infection with mumps.

In our study, extreme low effects of mean temperature, atmospheric pressure, and relative humidity, and an extreme high effect of wind speed were found among females with RR values less than 1, whereas no extreme effect was detected among males. This may be due to factors such as physiological gender differences and the discrepancy in behavior patterns [42]. For example, in extreme weather conditions, males are more active and will be more likely to play with friends, which will increase the contact rate with children infected with mumps. This shows that children should cut down on going to crowded places such as playgrounds in the active period of mumps from May to July in Guangzhou.

Our results showed a positive correlation before 1000.05 hPa, after which point the correlation was not statistically significant. However, previous studies showed different results. For instance, a study conducted in 10 cities in Guangxi province in China [20] reported that no significant relationship was found between atmospheric pressure and the incidence of mumps, whereas a study conducted in Beijing [17] showed that atmospheric pressure was negatively associated with mumps incidence. Unfortunately, limited studies are available regarding the underlying mechanism. This may be explained as follows. As the atmospheric pressure increases in the beginning, the cold air would enter and promote the spread of the virus, leading to high virus abundance in the atmosphere. After exceeding a certain value of atmospheric pressure, the effect mentioned above is offset by high wind speed. However, further studies should be conducted to explore the foundational mechanism in future.

Several limitations of our study should be acknowledged. At first, the data were only obtained in Guangzhou, southern China; hence, it cannot stand for other cities or countries. Secondly, we used meteorological data instead of the exposure conditions of individuals; this may lead to bias in our results. Further, we could not exclude the possibility that some potential confounding factors existed in our research, including host susceptibility, preventive measures, geographic factors, and population density. Moreover, data regarding human serum antibodies against mumps and information regarding mumps vaccination were unavailable in our study. Finally, we did not assess factors regarding air pollution which have been proven to affect the incidence of mumps [43]. Therefore, more studies should be undertaken to take these variables into consideration.

Conclusions

In general, compared to previous studies that focused on the effect of meteorological factors on mumps incidence, for the first time, we identified a significant nonlinear association between certain climatic variables and mumps incidence among children in Guangzhou with lag effects. At a certain corresponding range, mean temperature, atmospheric pressure, and relative humidity were positively correlated with the incidence of mumps among children, opposite to that of wind speed. Moreover, extreme effects of the variables mentioned above among mumps cases were detected in a subgroup analysis according to gender and age. These findings provide the underlying information to better understand the epidemic tendency of mumps. Based on our results, some measures could be implemented to minimize the occurrence of mumps. For example, preventative measures and health education should be strengthened in the temperature range of 10–23.6°C, and proper ventilation might be helpful in protecting children against infection with mumps. We also implied that children should cut down on going to crowded places such as playgrounds in the active period of mumps from May to July in Guangzhou. Our findings in this study will help improve the early warning system and reinforce the prevention and intervention of risk factors for mumps among children in Guangzhou.

The data and the R program of our study were uploaded as the supporting information file, which also included the data of subpopulation analyses.

(ZIP)

Click here for additional data file.

9 Jan 2020

PONE-D-19-31388

The roles of meteorological factors on mumps incidence among children in Guangzhou, Southern China

PLOS ONE

Dear Dr. Zhang,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Dear authors, your manuscript has been reviewed by two peer reviewers. Both requested Major Revisions to consider the manuscript to be published in Plos One.

I agree with all the notes made by the reviewers.

You must also review English. I suggest specialized companies like Editage and American Journal Experts.

In addition, I submit some mandatory corrections for the manuscript to be submitted to a new review round by the reviewers.

Therefore, I invite the authors to respond point-by-point to each comment made by the reviewers and myself (see below).

We would appreciate receiving your revised manuscript by Feb 10 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Paulo Eduardo Teodoro, Prof. Dr.

Academic Editor

PLOS ONE

Additional Editor Comments:

Dear authors, your manuscript has been reviewed by two peer reviewers. Both requested Major Revisions to consider the manuscript to be published in Plos One.

I agree with all the notes made by the reviewers.

You must also review English. I suggest specialized companies like Editage and American Journal Experts.

In addition, I submit some mandatory corrections for the manuscript to be submitted to a new review round by the reviewers.

Therefore, I invite the authors to respond point-by-point to each comment made by the reviewers and myself (see below).

- Abstract should be written according to Plos One models;

- It is necessary to include at the beginning of the Abstract and at the end of the Introduction what are the hypotheses of this research. This can be done in the form of a question;

- Keywords should be better chosen. They should not contain words that are in the title of the manuscript;

- There are several manuscripts addressing the theme "meteorological factors on mumps". In a quick search (https://www.sciencedirect.com/search/advanced?qs=meteorological%20factors%20mumps) I found at least seven similar manuscripts. Therefore, the authors should make clear in the Introduction what is the difference in the work done for papers that are already published. This needs to be improved in the Introduction;

- In the Material and Methods is necessary a map of the study area location;

- Although the authors employed robust statistical analyzes, further testing is still needed to improve the discussion of results. As the authors worked with an 18-year time series, it is necessary to check for changes in this time series with the nonparametric Man-Kendall and Pettitt tests. These tests are easily performed in the software R and may show if there was a tendency to increase or decrease in any meteorological variable and in the cases;

- Table 1 is important, but I would like to see a boxplot for these variables. Use the ggplot2 package;

- It is necessary to inform which test applied the Sperman correlations. In addition, I invite the authors to graphically express the results in Table 2 through the correlation network. It is a didactic way of representing this matrix. Can be done with the "qgraph" package in R;

- It is necessary to inform in the legend of Figures 2, 3 and 4 if the adjusted models were significant and which test was used for this;

- Discussion is very poor and needs to be improved. Authors should include findings from recent manuscripts I mentioned;

- In the conclusions, it is necessary to inform readers about the scientific advances that this manuscript has obtained in relation to the works already published. What are the proposals to minimize the occurrence of mumps in children by knowing the behavior of meteorological variables?

- The authors used only 35 references and most of them are old. In addition to being very little, recent references need to be included to demonstrate to readers that while there are many published manuscripts, the topic still needs to be studied.

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. In the ethics statement in the manuscript and in the online submission form, please provide additional information about the patient records used in your retrospective study.

Specifically, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent.

If patients provided informed written consent to have data from their medical records used in research, please include this information.

3. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dear authors,

The subject of the manuscript is interesting and topical, especially for the return of diseases previously eradicated or controlled in the last century. However, I found several weaknesses in the manuscript, for example, presentation of the results needs to improve, the discussion of the results does not cover other continents, only being restricted to Asia and Europe. As well as several gross errors throughout the manuscript, implying that the manuscript was not revised correctly. It is necessary to improve the quality of the figures to make them self explanatory. It is necessary to improve the conclusions of the manuscript.

Reviewer #2: Dear Authors,

The manuscript makes an interesting based on interaction between mumps and meteorological variables. It is believed that more information on the subject can still be extracted, even in face of the limitations described by authors.

On this aspect, some points need to be improved throughout the text, I believe they should include the references of R software, as well as dlnm package, both described on manuscript.

The introduction and materials and methods are well described.

Regarding the results, I have some suggestions for improvement:

1) Replacement of Figure 1 with a boxplot of mumps cases on an annual and monthly basis.

2) The other variables would be displayed in Figure 2, with monthly boxplots, making the visualization of the results much more understandable in some passages of the text, exploring the maximum and minimum.

3) The old Figure 2 (which will be for Figure 3) could include the intensities, not only leaving the color red, this would show the interaction between them.

4) Improve the image resolution of all images, as they are of low quality.

5) Paragraph preceding Figure 3, correct the pHa for HPa, on page 11.

Well, from these improvements and implementations, the article will be able to be approved.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

Submitted filename: PONE-D-19-31388_R1.pdf

Click here for additional data file.

20 Feb 2020

Dear Editor,

We acknowledge with thanks the receipt of the comments of the reviewer. These comments/requirements were highly beneficial in the modification of the manuscript. The manuscript was revised according to all these comments. All modifications and/or corrections are highlighted by using the track changes mode. We would like to thank Editage (www.editage.cn) for English language editing. A point-to-point response to the reviewers’ comments was attached. We appreciate you kindly offer the opportunity to transfer our manuscript.

Additional Editor Comments

Question No1: Abstract should be written according to Plos One models;

Response to the question No.1: We re-wrote the Abstract according to Plos One models.

Question No.2：It is necessary to include at the beginning of the Abstract and at the end of the Introduction what are the hypotheses of this research. This can be done in the form of a question;

Response to the question No.2: We added the hypotheses of this research in the article ,L81-86“However, the nonlinear and lag effects of climatic factors on the transmission among children, who are the main population affected by mumps, are still unclear at present. A study conducted in Japan explored the linear relationship between meteorological factors and mumps incidence among children via negative binomial regression analysis (24). What are the roles of meteorological factors on mumps incidence among children? There is an urgent need to explore these nonlinear relationships using lag effects..”

Question No.3： Keywords should be better chosen. They should not contain words that are in the title of the manuscript;

Response to the question No.3: Thanks for your question. As your suggestion, the Keywords were revised as following:“distributed lag nonlinear models, climatic factors, effect”.

Question No.4：There are several manuscripts addressing the theme "meteorological factors on mumps". In a quick search (https://www.sciencedirect.com/search/advanced?qs=meteorological%20factors%20mumps) I found at least seven similar manuscripts. Therefore, the authors should make clear in the Introduction what is the difference in the work done for papers that are already published. This needs to be improved in the Introduction;

Response to the question No.4: Thanks for your question. As your suggestion, we described the difference of the similar researches on mumps, and the section were revised as L68-86.

Question No.5： In the Material and Methods is necessary a map of the study area location;

Response to the question No.5: The map of the study area location was added in the Material and Methods.

Question No.6： Although the authors employed robust statistical analyzes, further testing is still needed to improve the discussion of results. As the authors worked with an 18-year time series, it is necessary to check for changes in this time series with the nonparametric Man-Kendall and Pettitt tests. These tests are easily performed in the software R and may show if there was a tendency to increase or decrease in any meteorological variable and in the cases;

Response to the question No.6: We use the nonparametric Man-Kendall and Pettitt tests to check for changes in our time series data. And the result was shown as Table 1

Question No.7：Table 1 is important, but I would like to see a boxplot for these variables. Use the ggplot2 package;

Response to the question No.7：Thanks for your suggestion. We used the boxplot (Fig 3.) to describe these meteorological variables instead of the original table.

Question No.8：It is necessary to inform which test applied the Sperman correlations. In addition, I invite the authors to graphically express the results in Table 2 through the correlation network. It is a didactic way of representing this matrix. Can be done with the "qgraph" package in R;

Response to the question No.8: Thanks for your suggestion. We applied the correlation network(Fig 5.)to graphically express the results in the original Table 2.

Question No.9：It is necessary to inform in the legend of Figures 2, 3 and 4 if the adjusted models were significant and which test was used for this.

Response to the question No.9: Based on the AICs, we selected the smallest AIC to different meteorological variables to structure the best models. We showed the RR and 95% confidence interval (95%CI) of the original figure 2，3 and 4. Meantime, we could see the RR and 95% CI in the original figure 3 and 4 (The red lines represent mean relative risks and the grey regions represent 95%CIs.) If the 95% CI include “1” as the RR value, there is not significant difference. Otherwise, it means that it’s significantly different. It equals to the P value <0.05.

Question No.10：Discussion is very poor and needs to be improved. Authors should include findings from recent manuscripts I mentioned;

Response to the question No.10: Thanks for your advice. We got some recent manuscripts the reviewer mentioned and other new article into reference added to 43 articles, and revised the discussion.

Question No.11：In the conclusions, it is necessary to inform readers about the scientific advances that this manuscript has obtained in relation to the works already published. What are the proposals to minimize the occurrence of mumps in children by knowing the behavior of meteorological variables?

Response to the question No.11:

In the conclusions, scientific advance was informed as L358-361 “In general, compared to previous studies that focused on the effect of meteorological factors on mumps incidence, for the first time, we identified a significant nonlinear association between certain climatic variables and mumps incidence among children in Guangzhou with lag effects.” And L363-365“Moreover, extreme effects of the variables mentioned above among mumps cases were detected in a subgroup analysis according to gender and age.” Due to the results of our study, some proposals were recommended to minimize the occurrence of mumps among children. L367-371 “For example, preventative measures and health education should be strengthened in the temperature range of 10–23.6°C, and proper ventilation might be helpful in protecting children against infection with mumps. We also implied that children should cut down on going to crowded places such as playgrounds in the active period of mumps from May to July in Guangzhou.”

Question No.12：The authors used only 35 references and most of them are old. In addition to being very little, recent references need to be included to demonstrate to readers that while there are many published manuscripts, the topic still needs to be studied.

Response to the question No.12: Thanks for your kindly reminder, We reviewed the recent references and revised the introduction, and demonstrated the scientific advance and the difference between our study and previous researches. Firstly our study use the DLNMs to explore the nonlinear relationships with lag effects between meteorological variables and mumps cases. Secondly we firstly used the DLNMs to analyze the meteorological effects on mumps cases among children. Finally, we analyze the effect by subpopulation by sex and age among children. This detail could be seen in the “introduction and discussion”.

“

Reviewer #1:

The subject of the manuscript is interesting and topical, especially for the return of diseases previously eradicated or controlled in the last century. However, I found several weaknesses in the manuscript, for example, presentation of the results needs to improve, the discussion of the results does not cover other continents, only being restricted to Asia and Europe. As well as several gross errors throughout the manuscript, implying that the manuscript was not revised correctly. It is necessary to improve the quality of the figures to make them self explanatory. It is necessary to improve the conclusions of the manuscript.

Response to the question of reviewer 1：Thanks for your kindly suggestion. We review the recent article and add some researches from Canada and Mexico into the discussion. We reviewed English by Editage company to avoid gross errors in our article. We also revised and improved the conclusions of the manuscript, the scientific advance was mentioned in the conclusion(L358-361, L363-365), and the control measures to reduce the occurrence of mumps among children were recommended too( L367-371).

Reviewer #2:

The manuscript makes an interesting based on interaction between mumps and meteorological variables. It is believed that more information on the subject can still be extracted, even in face of the limitations described by authors. On this aspect, some points need to be improved throughout the text, I believe they should include the references of R software, as well as dlnm package, both described on manuscript. The introduction and materials and methods are well described. Regarding the results, I have some suggestions for improvement:

Question No.1：Replacement of Figure 1 with a boxplot of mumps cases on an annual and monthly basis.

Response to the Question No.1：Thanks for your suggestion, we replaced the figure 1 with a boxplot of mumps cases on annual and monthly basis(Fig 2.).

Question No.2：

The other variables would be displayed in Figure 2, with monthly boxplots, making the visualization of the results much more understandable in some passages of the text, exploring the maximum and minimum.

Response to the Question No.2：Thanks for your suggestion, we replaced the figure 2 with monthly boxplots, exploring the maximum and minimum(Fig 3.).

Question No.3：

The old Figure 2 (which will be for Figure 3) could include the intensities, not only leaving the color red, this would show the interaction between them.

Response to the Question No.3：Thanks for your suggestion, we tried to change the old figure 3 with the intensities, however, we thought the original one would be better.

Question No.4：

Improve the image resolution of all images, as they are of low quality.

Response to the Question No.4：thanks for your suggestion, we fix the image resolution of all images due to the guideline in Plos One Journal.

Question No.5：

Paragraph preceding Figure 3, correct the pHa for hPa, on page 11. Well, from these improvements and implementations, the article will be able to be approved.

Response to the Question No.5：Thanks for your advice, We correct the pHa for hPa, on original page 11.

Submitted filename: Response to the reviewers.docx

Click here for additional data file.

23 Mar 2020

PONE-D-19-31388R1

The roles of meteorological factors on mumps incidence among children in Guangzhou, Southern China

PLOS ONE

Dear Mr Zhang,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

We would appreciate receiving your revised manuscript by May 07 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Paulo Eduardo Teodoro, Dr.

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dear Authors.

The manuscript has improved significantly. However, some details need to be incorporated and some corrections in the figures and tables. All corrections follow from the document.

Reviewer #2: According to a new analysis carried out on manuscript about the mumps incidence in Guangzhou City - China, note a significant improvement in the writing of the text.

However, there are still some questions that can be answered:

1) Does the impact of the variables used influence similarly for each age group or sex? It is believed to be interesting information to be explored.

2) What is the main variable for the development of mumps? The results are presented throughout the text, with the data identified, so that you do not mention the most important variable in this context.

3) On line 142, create the article of the dlnm package.

4) Table 1 deserves to be better explored, because it was reproduced in the text. And based on the trend signal, which is significant, what is the interaction between meteorological variables and the mumps?

5) On line 187, an ideal word would not be correlation, but interaction.

6) On lines 204 and 205, how did you get confused. Would the RR be 60%?

7) In Figure 8, correct the word "effet" for "effect", found in the central part.

8) In Table 2, include a valve on high-effect atmospheric pressure, from 088 to 0.88.

After these changes, further details should be incorporated into the conclusions and the review. In this way, with these problems solved, the article can be accepted for a journal.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

Submitted filename: PONE-D-19-31388_R1_RV.pdf

Click here for additional data file.

8 Apr 2020

Response to Reviewers

Dear Editor,

We acknowledge with thanks the receipt of the comments of the reviewer. These comments/requirements were highly beneficial in the modification of the manuscript. The manuscript was revised according to all these comments. All modifications and/or corrections are highlighted by using the track changes mode. We would like to thank Editage (www.editage.cn) for English language editing. A point-to-point response to the reviewers’ comments was attached. We appreciate you kindly offer the opportunity to transfer our manuscript.

Reviewer #1:

Thanks for your comments. We checked the article again and corrected the mistakes. For example, in Figure 8, we corrected the word "effet" for "effect", found in the central part.

Reviewer #2:

Question No.1：Does the impact of the variables used influence similarly for each age group or sex? It is believed to be interesting information to be explored.

Response to the Question No.1：Thanks for your suggestion, we analyzed the cumulative extreme effects of meteorological variables on mumps cases of children by sex and age at table 3. “In the analyses by subpopulation, the extreme low effects of temperature, atmospheric pressure, and relative humidity, and the extreme high effect of wind speed showed statistical significance in the female population, but no significant extreme effect was observed in the male population. The extreme low effect of temperature was observed between 4-6 years group (RR=0.25, 95%CI: 0.11-0.60) and 15-17 years group (RR=0.01, 95%CI: 0.00-0.57). The extreme high effect of atmospheric pressure was revealed at the 4-6 years group (RR=0.46, 95%CI: 0.21-0.98)”

Question No.2：

What is the main variable for the development of mumps? The results are presented throughout the text, with the data identified, so that you do not mention the most important variable in this context.

Response to the Question No.2：

Thanks for your suggestion. We structured different model to different variables. Each variable had its own characteristic to the development of mumps. So it was hard to say which variable was more important. The strongest interaction was observed between temperature and mumps cases, and tendency was easy for the public to get. Therefore, if we much choose one of the variables as the most important factors, we will choose the temperature.

Question No.3：

On line 142, create the article of the dlnm package.

Response to the Question No.3：

Thanks for your suggestion, we added the reference about DLNM package into the article.

Question No.4：

Table 1 deserves to be better explored, because it was reproduced in the text. And based on the trend signal, which is significant, what is the interaction between meteorological variables and the mumps?

Response to the Question No.4：

Thanks for your advice. We add the content to explore the table 1, “The variables of DTR, rain, pressure, wind, relative humidity were statistically significant. Wind and relative humidity had a rising tendency, whereas the DTR, rain and pressure had a decrease tendency. No tendency was observed among the variables of cases, temperature and sunshine hours.”

Fig 5 shows the interaction network between meteorological factors and mumps cases among children, the strongest interaction was observed between temperature and mumps cases. Temperature, sunshine hour, relative correlation and aggregate rainfall had a positive interaction with mumps cases, whereas atmosphere pressure, wind speed and DTR had a negative interaction with mumps cases.

Question No.5：

On line 187, an ideal word would not be correlation, but interaction.

Response to the Question No.5：

We change the interaction instead of the correlation on line 197, thanks for your advice.

Question No.6：

On lines 204 and 205, how did you get confused? Would the RR be 60%?

Response to the Question No.6：

Maybe the expression made confusion. I revised the article as “However, the RRs just had a significantly increasing trend before the atmosphere pressure as 992 hPa and the relative humidity as 60%, respectively.”

Question No.7：

In Figure 8, correct the word "effet" for "effect", found in the central part

Response to the Question No.7：

We are sorry for this mistake. We revised the figure 8 and correct the word “effect”.

Question No.8：

In Table 2, include a valve on high-effect atmospheric pressure, from 088 to 0.88.

Response to the Question No.8：

We are sorry for this mistake. We corrected the 088 to 0.88.

Thanks again.

Submitted filename: Response to the reviewers.docx

Click here for additional data file.

13 Apr 2020

The role of meteorological factors on mumps incidence among children in Guangzhou, Southern China

PONE-D-19-31388R2

Dear Dr. Zhang,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

With kind regards,

Paulo Eduardo Teodoro, Dr.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors made all the corrections requested by the reviewers and me. The manuscript has substantially improved over the first version submitted and is in a condition to be accepted.

Reviewers' comments:

16 Apr 2020

PONE-D-19-31388R2

The role of meteorological factors on mumps incidence among children in Guangzhou, Southern China

Dear Dr. Zhang:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

For any other questions or concerns, please email plosone@plos.org.

Thank you for submitting your work to PLOS ONE.

With kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Professor Paulo Eduardo Teodoro

Academic Editor

PLOS ONE

Table 1

The results of the Man-Kendall and Pettitt tests for the meteorological variables and mumps cases among children in Guangzhou, 2014–2018.

variables	P	S	change-point number	change-point	P
case	0.3	+	1542	2018/3/22	<0.01
temperature	0.19	+	129	2014/5/9	<0.01
DTR	<0.01	-	414	2015/2/18	<0.01
rain	<0.01	-	986	2016/9/12	<0.01
pressure	<0.01	-	482	2015/4/27	<0.01
wind	<0.01	+	371	2015/1/6	<0.01
relative humidity	<0.01	+	794	2016/3/4	<0.01
Sunshine hours	0.88	-	674	2015/11/5	0.02

# S: ‘+’ means a rise tendency, ‘-‘means a decrease tendency.

Table 2

The extreme effects of meteorological variables on the incidence of mumps among children along the lag days in Guangzhou, 2014–2018.

Meteorological variables	Lag day	High effect (97.5%)		Lag day	Low effect (2.5%)
		RR	95%CI		RR	95%CI
Mean temperature	/	/	/	0	0.88	0.83–0.93
Atmospheric pressure	0	0.88	0.82–0.94	/	/	/
Wind speed	0	0.94	0.89–0.98	/	/	/
Relatively humidity	2	0.96	0.94–0.99	2	0.96	0.93–0.99

Table 3

The cumulative extreme effects of meteorological variables on mumps cases of children by sex and age.

Variables	Mean temperature				Wind speed				Relative humidity				Atmospheric pressure
	low effect		high effect		low effect		high effect		low effect		high effect		low effect		high effect
	RR	95%CI	RR	95%CI	RR	95%CI	RR	95%CI	RR	95%CI	RR	95%CI	RR	95%CI	RR	95%CI
total	0.56	0.32–0.99	0.99	0.70–1.40	0.77	0.47–1.28	0.64	0.40–1.01	0.76	0.61–0.94	0.89	0.67–1.17	0.70	0.49–0.99	0.75	0.45–1.24
male	0.88	0.44–1.73	0.91	0.59–1.39	0.76	0.41–1.41	0.88	0.50–1.56	0.95	0.73–1.23	1.06	0.75–1.49	0.87	0.56–1.34	0.81	0.43–1.50
female	0.23	0.10–0.62	1.12	0.66–2.02	0.77	0.74–1.71	0.34	0.16–0.72	0.50	0.35–0.72	0.64	0.41–1.00	0.47	0.26–0.83	0.64	0.28–1.45
<4years	1.83	0.60–5.65	1.40	0.69–2.83	0.99	0.36–2.71	0.74	0.29–1.87	0.73	0.48–1.11	0.70	0.39–1.24	0.54	0.26–1.09	0.97	0.37–2.55
4–6 years	0.25	0.11–0.60	1.01	0.58–1.75	0.68	0.31–1.49	0.51	0.25–1.05	0.77	0.56–1.07	1.28	0.83–1.96	0.81	0.46–1.42	0.46	0.21–0.98
7–13 years	0.82	0.32–2.10	0.83	0.48–1.44	0.79	0.35–1.80	0.81	0.37–1.76	0.76	0.52–1.11	0.72	0.45–1.14	0.73	0.41–1.30	1.25	0.51–3.05
14–17 years	0.01	0.00–0.57	0.18	0.01–2.74	0.35	0.01–16.28	0.05	0.00–2.18	0.48	0.07–3.29	0.38	0.05–3.09	0.20	0.01–2.66	0.08	0.00–3.08