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. 2022 Jun 24;17(6):e0268865. doi: 10.1371/journal.pone.0268865

Increasing incidence of reported scabies infestations in the Netherlands, 2011–2021

Babette van Deursen 1,*, Mariëtte Hooiveld 2,3, Susan Marks 4, Ingrid Snijdewind 4, Hans van den Kerkhof 2, Bas Wintermans 5, Ben Bom 2, Barbara Schimmer 2, Ewout Fanoy 1
Editor: Joël Mossong6
PMCID: PMC9231777  PMID: 35749401

Abstract

Introduction

Several Public Health Services and general practitioners in the Netherlands observed an increase in scabies in the Netherlands. Since individual cases of scabies are not notifiable in the Netherlands, the epidemiological situation is mostly unknown. To investigate the scabies incidence in the Netherlands, we described the epidemiology of scabies between 2011 and 2021.

Methods

Two national data sources were analysed descriptively. One data source obtained incidence data of scabies (per 1,000 persons) of persons consulting in primary care from 2011–2020. The other data source captured the number of prescribed scabicides in the Netherlands from 2011–2021. To describe the correlation between the incidence of diagnoses and the number of dispensations between 2011 and 2020, we calculated a correlation coefficient.

Results

The incidence of reported scabies has increased by more than threefold the last decade (2011–2020), mainly affecting adolescents and (young) adults. This was also clearly reflected in the fivefold increase in dispensations of scabicide medication during 2011–2021. The incidence and dispensations were at an all-time high in 2021. We found a strong correlation between the reported incidence and the number of dispensations between 2011 and 2020.

Conclusions

More awareness on early diagnosis, proper treatment and treatment of close contacts is needed.

Introduction

Scabies is officially categorized as a neglected tropical disease. In recent years scabies manifestations are increasing in numbers in Europe [14]. Global epidemiological data is rather scarce as it is not notifiable in many countries [5]. Scabies is mainly transmitted by prolonged skin-to-skin contact or by contact with infested items such as bedding and clothes. In the past years, the general practitioners (GPs) observed a gradual increase of scabies diagnoses in the Netherlands. Other (neighbouring) European countries also reported an increase of scabies infestations in their countries in recent years [14]. Individual cases of scabies in the general population are not notifiable in the Netherlands. It is only notifiable to the Public Health Service (PHS) when diagnosed in persons who works, lives or attends vulnerable settings such as kindergartens, schools, and care or cure institutions [6]. In the Netherlands, topical permethrin (5%) or topical benzyl benzoate (25%) is the preferred course of treatment for scabies. Another course of treatment is systemic by prescribing oral ivermectin (3mg) when topical treatment has failed or is contra-indicated.

Several PHS suggested anecdotally a recent increase in scabies notifications since the autumn of 2021. The number of notified outbreaks does not represent the true burden of infections in the population but are the tip of the iceberg. The epidemiological situation of scabies in the Netherlands is not well-known or even described. To investigate the scabies incidence, we analysed two national data sources to describe the epidemiology of scabies in the Netherlands between 2011 and 2021.

Methods

Two separate national data sources were used to describe the epidemiological situation of scabies among the general population in the Netherlands during 2011–2020. To describe the correlation between the incidence of diagnoses and the number of dispensations between 2011 and 2020, we calculated a correlation coefficient (Pearson’s r).

Scabies diagnoses reported by general practitioners

The first data source contains electronic records of scabies diagnoses from a national representative primary care database of GPs hosted by Nivel (the Netherlands Institute for Health Services Research) [7]. In the Netherlands, general practitioners are the first point of contact for health care and there are no private clinics who provide primary care. We obtained incidence data of scabies (per 1,000 persons) of persons consulting general practitioners from 2011–2020 by age group and sex during the study period and performed descriptive analyses. We investigated the trend of the incidence by years and by age group. Most institutionalised residents are not taken into consideration in these registrations, considering other physicians are usually responsible for their consultations. Furthermore, the incidence of 2021 was not calculated and available at the time of our study, thus could not be taken into consideration in our analysis.

Recorded prescriptions and over-the-counter sales of scabicides

The second database contains pharmaceutical data collected by the Dutch Foundation for Pharmaceutical Statistics (SFK) on the number of prescribed and over-the-counter scabicides in the Netherlands [8]. Data on dispensations of prescribed drugs is anonymously gathered from more than 98% of the community pharmacies in the Netherlands. We obtained the number dispensations of scabicides from SFK from 2011–2021, which consisted of type of supplied scabicide (ivermectin (3mg), permethrin (5%) and benzyl benzoate (25%)), sex and age of the patient. This data did not include any information on indication, so these dispensations could be prescribed for other indications than scabies. We described the SFK data by sex and age group and by month. Prescriptions of institutionalised residents are not gathered by SFK.

Ethical statement

This study used routinely collected, anonymized and aggregated data, which cannot be traced back to individual patients. Surveillance of infectious diseases is one of the legal tasks of the Public Health Service as described under the Public Health Act, and do not require separate medical ethical clearance.

Results

Reported scabies diagnoses

The incidence of scabies diagnoses per 1,000 persons per year recorded by GPs in 2011 was 0.6 and increased more than 4-fold to 2.6 in 2020 (Fig 1). No differences were observed between men and women. The highest incidence was among 15–29-year-old persons, especially among 20–24-year-olds. The increase started in 2013 and continued the following years. There was a stabilisation in incidence in 2018 yet increased again in 2020 to 2.6 scabies diagnoses per 1,000 persons (per year).

Fig 1. The incidence of scabies diagnoses per 1,000 persons as recorded by the general physicians from 2011–2020, the Netherlands.

Fig 1

Recorded scabicides prescriptions and over-the counter sales by public pharmacies

A total of 702,317 scabicides (permethrin, ivermectin and benzyl benzoate) were dispensed between 2011 and 2021. In 14% of the dispensations, sex of the patient was not registered. Slightly more males bought a scabicide then women (53% vs. 47%) and the male-to-female ratio remained stable during the study period. The most common prescribed scabicide was permethrin (>70%).

In 2011, the total number of dispensations of all scabicides was 28,300 and increased to a total of 142,622 in 2021, which is more than a 5-fold increase in a decade. In more detail: since the end of 2013, the number increased gradually until 2018 and became more pronounced during 2019 and especially peaked in 2021 (Fig 2). In the last months of 2021, the number of permethrin dispensations even reached an all-time high with an increase of >200% from September–December. Furthermore, the increase in dispensations of permethrin indicates a seasonal pattern with a clear peak in autumn and winter months. We found a strong correlation between the number of dispensations and reported incidence between 2011 and 2020 (r = 0.98; p<0.001).

Fig 2. Number of dispensations of scabicides (permethrin, ivermectin and benzyl benzoate) per month between 2011–2021, the Netherlands.

Fig 2

Most of the permethrin and ivermectin dispensations were handed out to patients in the age category of 20–25 years (19%), followed by 15–20 years (9%) and 25–30 years (8%) (Fig 3). Approximately 70% of the dispensations was permethrin in each age group, except for 0–15-year-olds where it was around 80%. The trend of dispensations by age group was similar to the trend seen in Fig 2. The ‘unknown’ group (18%) among permethrin dispensations are most likely over-the-counter sales, since no prescription for this drug is required. For ivermectin, the ‘unknown’ dispensations are most likely from doctors/general practitioners to other colleagues or to use as stock.

Fig 3. Total number of dispensations of permethrin and ivermectin by age group, 2011–2021, the Netherlands.

Fig 3

Discussion

The incidence of reported scabies in the general population of the Netherlands has increased by more than threefold the last decade. Incidence of diagnoses made by general practitioners started to increase gradually since 2013 and continued the following years, especially among adolescents and (young) adults. The number of dispensations of scabicides reported a more than fivefold increase from 2011–2021. The reported incidence of scabies and the number of dispensations of scabicides between 2011 and 2020 were strongly correlated. Most of the dispensations were permethrin, mainly dispensed to 20–25-year-olds and mostly during autumn and winter season. The observed peak in ivermectin prescriptions in 2014–2015 was due to several large outbreaks in healthcare facilities with a high number of contacts preventively treated [9].

It is interesting to assess the impact of the COVID-19 pandemic on scabies incidence, since almost all notifiable infectious diseases decreased during the COVID-19 pandemic due to less transmission as underreporting and underdiagnosing [10]. On the contrary, there was a remarkable sharp increase of incidence and dispensations of scabicides since 2020, mainly in adolescents and (young) adults. There seems no limiting effect of the general social distancing measures on scabies incidence. It is suggested that some of the measures had the opposite effect among the adolescents and young adults. For example, a curfew between 23 January 2021 and 28 April 2021 was in place in the Netherlands, which could have led to more sleepovers and thus more transmission. The recent trends of scabies incidence in other European countries during the COVID-19 pandemic is unclear, as no peer-reviewed studies have been published beyond the year 2019.

The observed increase in incidence corresponds with the trend in other European countries, such as Germany, Norway, Croatia, Poland, and Spain [14,11]. Although each country has slightly different surveillance systems in place or used other data sources than our study, they all still reported an increase in the last years. The increase in number of dispensations of scabicides could partly explained by population growth in recent years. The increasing trends were most striking in adolescents and (young) adults and was also timed roughly similarly. It is remarkable that these countries observed a comparable seasonal trend in autumn and winter season [14,11,12]. It can be suggested that the seasonal trend is caused by more contact during cold and dry seasons [12].

Since skin-to-skin contact is the common transmission route for scabies, the observed increase among adolescents and (young) adults could be explained by more exposure due to more contacts than older generations [1,4]. We did not see a difference in incidence between males and females, however more males bought a scabicide medication than females. In Germany, more males were diagnosed with scabies in recent years and it was suggested that young adult males have the highest social connectivity [4]. It is also known that, concerning scabies, medical and outbreak policy adherence (such as washing of clothing and bed linen) among adolescents and young adults are generally lower than for older adults, which can lead to treatment failure [13]. Other studies suggest that the increase could be partly explained by frequent introductions from tourists or asylum seekers [2].

Increasing resistance of mites to scabicides could be an explanation on the increasing trend [14]. Unfortunately, we do not have insight in prevalence of scabicide resistance as diagnostic tools are not yet in place. Further research on resistance, for example by developing diagnostic molecular tools, is necessary to fully understand the drivers of the increasing trend.

This study was based on persons who consulted their GP and/or who bought scabicide medication at the pharmacy, which means that institutionalised residents are not included. However, most of the infested persons live and work outside these facilities. The reported incidence of 2021 was not calculated and still unknown, therefore we could not take it into consideration in our study. Also, we did not investigate the number of reported outbreaks to the PHS because the criteria for notifying scabies in vulnerable settings were adapted in 2019 and therefore not comparable with recent years. It is possible that the increase in dispensations is caused by patients with multiple prescriptions due to treatment failure. However, we only obtained data on the total number of dispensations of scabicides and not number of patients, so we could not investigate if the increase is explained by treatment failure, re-infestations or by more patients with scabies infestations. Additionally, we do not obtain the data of the other 2% of community pharmacies since they are not included in the SFK dataset. Also, permethrin can be bought at drugstore chains in the Netherlands, so the number of all dispensations is presumably higher than presented. Another limitation is that SFK does not report the indication for the prescription or dispensation, so it is possible that some of the dispensations were not related to scabies. For example, ivermectin could also be prescribed as a drug against COVID-19, while it is proven not to be effective [15,16]. This could explain the sudden rise of ivermectin dispensations at the end of 2021.

The surveillance of scabies is scattered, and an integration of data sources would be wise to improve since it is not notifiable for individual cases. Some elements are missing, such as social background of patients, source of infestation and transmission routes of mites within and between countries. Skin material scraped from suspect lesions or bed linen can be used as diagnostic tool using PCR [17]. Positive specimens can be molecularly typed and combined with epidemiological information, which can generate insight in transmission chains within the population and identify circulation within social communities or facilities. These deeper understandings of hotspots and transmission routes are informative for effective anti-scabies measures and policy.

In summary, the incidence of scabies and the dispensations of scabicide medications in the Netherlands have increased in the last decade, especially among adolescents and (young) adults. As this scabies increase is observed in several more European countries, a robust integrated approach is needed. The surveillance of scabies should be improved by combining several available databases and by collecting more data on social background and source of infestation. The potential use of molecular typing to detect clusters and transmission chains should be explored. Higher awareness of suspected clinical symptoms among the younger population and physicians is necessary to allow early diagnosis and treatment and thus stop transmission, so therefore we recommend better training and clear medical guidelines for physicians. In addition to these advices, it is important to emphasize proper treatment including washing of clothing and bed linen. Furthermore, the treatment should not only be focused on the individual patient, but also on close contacts.

Supporting information

S1 Database

(DOCX)

S1 File

(XLSX)

Acknowledgments

The authors would like to thank other colleagues of the Public Health Service and National Institute for Public Health and the Environment for their input and advice. This study has been approved according to the governance code of Nivel Primary Care Database, under number NZR-00321.072.

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

This study was supported by the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment (RIVM), The Netherlands in the form of an unrestricted grant.

References

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Decision Letter 0

Joël Mossong

11 Mar 2022

PONE-D-22-04888Increasing incidence of scabies infestations in the Netherlands, 2011 – 2021PLOS ONE

Dear Dr. van Deursen,

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Reviewer #1: General comment

Overall, even if the topic is quite relevant, the paper is quite poor. The intro and methods sections need to be improven and completed.

Abstract

The main objective is too ambitious, a research shouldn´t be triggered by an assumption, please rephrase

Introduction

Overall, the introduction is quite short. I would recommend to add a short description on disease background, not only on clinics and current challenges (i.e. treatment resistances) but also on its worldwide epidemiology (including the fact that it´s an NTD)

Line 36: Is it possible to sustain this information (“general practitioners (GPs) observed a gradual increase of scabies diagnoses in 37 the Netherlands”) with some references?

Line 40: Are the PHS notified of individuals attending this kind of vulnerable setting? Or are you referring to aggregate/outbreak data? Please specify

Line 46: same comment that above. The main objective is too ambitious, a research question cannot be based in previous assumptions

Methods

Line 55: Would it be possible to include some information of population coverage?

Is there any other available data source to understand the situation on institutionalized residents? Why the authors did not analyze the information notified to the PHS on vulnerable settings?

Which was the study period for this first data source? Does it gather info also from private clinics?

Line 58. Please describe in detail which sort of descriptive analysis was performed. Results by sex are also given in the results section, but this is not explained in methods.

Line 67. Are these treatments only used for scabies? Please specify

Further spatial analysis could have been performed based on the pharma data

Ethical statement: There is a reference to outbreak investigations, but this information is not included in the analysis, is this correct?

Results

This section is a bit poor. A table with some additional data is recommended.

Was the study period the same? Did you find any temporal relationship between both databases?

Line 87. This last sentence should be placed in the discussion section, as it´s not referring to study results.

A bit more advanced analytical techniques (such as linear regression, joint point analysis) could help to better assess the temporal trend of this disease

Line 105-108: this belong to the discussion section

Discussion

Line 124. This first statement cannot be based on the provided results (due to the limitations of both data sources)

Line 131 It is probable that the incidence of notifiable diseases has decreased during the COVID-pandemic, but also there might have been underreporting. Regarding scabies, and given its transmission mode (which should be better explained in the introduction section), the impact of the COVID pandemic might be the opposite (somehow, homes became close institutions). Also, the high burden on GPs might have also affect the attendance and follow-up of patients, worsen the situation.

Line 139. What is the relationship between population growth and increase in scabies incidence? Is this related to worst health conditions and poverty?

Regarding the increasing trend in young population, is it possible that sexual transmission of scabies has also increased?

Line 154. I don´t think this is an explanation of COVID times, on the contrary, incidence should have decreased.

Line 157. This paragraph does not discuss the study results. Please rephrase or delete

Line 163. Even if you don´t have info on resistance, an increase in other treatments rather than permethrin could had supported this hypothesis.

Line 180. You may add a reference to EMA recommendations against the use of ivermectin for COVID-19 EMA advises against use of ivermectin for the prevention or treatment of COVID-19 outside randomised clinical trials | European Medicines Agency (europa.eu)

Line 197. Looking at the incresaing number of cases, would you also recommend better training, medical guidelines, etc for primary health care centres?

Reviewer #2: The authors present an increasing incidence of scabies infestations in the Netherlands during 2011 – 2021. The manuscript confirms what previously reported by other countries in Europe, as well as providing additional information during more recent years under the pandemic context. The manuscript is interesting and deserve to be published, here below some points that could improve clarity and the quality of the manuscript.

Language revision, preferably by a native speaker, would improve the quality of the manuscript. For example, the use of the word ‘several’ would fit better than ‘multiple’ in some sentences. In the title ‘scabies diagnoses by general practitioners’, I would add the word ‘reported’ before ‘by’. Similarly for the title, ‘Scabicides prescriptions and over-the counter sales by public pharmacies’, I would add ‘reported’ or ‘recorded’. Line 150, I would replace ‘since’ with ‘in’

Introduction, line 44, I think the sentence ‘There are complexities concerning scabies surveillance: clinical recognition and diagnostic tools such as microscopy, dermatoscopy and PCR have sensitivity issues’ is a bit out of place since it is not a notifiable disease in the Netherlands, and does not connect well the sentences before and after. It could be deleted from here and be used in the discussion part when relevant.

Methods part, line 52, it is mentioned ‘2011-2020’ while in the introduction and abstract it is mentioned 2011-2021 period. This is confusing to the reader. My understanding is that the data on scabies diagnosis was available until 2020. If this is the case, authors should clarify somewhere in the manuscript the reason why data from 2021 were not included.

Methods part, line 68, could you specify more in details the type of treatment? E.g., permethrin cream? Ivermectin tablets? Is It possible to add in introduction which treatments are used in the Netherlands?

Ethical statement, line 73, the authors stated, ‘outbreak investigations of notifiable diseases such as scabies’ while in line 38 ‘cases of scabies are not notifiable’. I would suggest rephrasing to make it more understandable what you mean in the ‘ethical statement’ section.

Results, line 87, ‘Remarkably, this was despite the COVID-19 pandemic and its corresponding control and hygiene measures.’ I think it is a very interesting results, do you have any hypothesis on this aspect? Could you add a sentence or short paragraph in discussion section providing an explanation/hypothesis of this phenomenon based on your experience?

Results, line 83, ‘No differences were observed between men and women.’ while line 97 ‘Slightly more males bought a scabicide then women’. Is there a possible explanation for this difference?

Do data on scabies diagnosis include recurrent cases (re-infestation) or it was possible to identify records from the same patient in your dataset? This need to be clarified and added as limitation if was not possible to look at re-occurrent cases.

It is mentioned in line 59 ‘Most institutionalised residents are not taken into consideration in these registrations, considering other physicians are usually responsible for their consultations.’ What about the database on pharmaceutical data, does it exclude as well the treatment of institutionalized residents? If not, this need to be clarified and/or added as limitation.

Line 180 ‘ivermectin could also be prescribed as a drug against COVID-19, while it is proven not to be effective (15). This can explain the sudden rise of ivermectin dispensations at the end of 2021.’ Including data on scabies diagnosis in 2021 would allow to have more solid conclusion. If you did not compare it with scabies diagnosis data, I would amend ‘this can explain’ with ‘this could explain’.

Line 183 and line 193, the authors mention ‘surveillance’ but it is not a notifiable disease, could you clarify and rephrase it if needed?

Figure 1: Did you try to compare the incidences level reported in the Netherlands with the ones reported in other countries? Anything to highlight? A sentence/paragraph on this aspect can be added in the discussion providing authors’ perspective.

Figure 2: does the 3-months average add something to the interpretation of results or discussion. If not, I would simplify it deleting them for permethrin and ivermectin.

I would also integrate figure 1 with figure 2, visually comparing the two datasets on scabies diagnosis and dispensations of scabicides. You could also use number of diagnoses instead of incidence, if this will improve the data visualization. The values on incidence per year are available in supplementary material in any case.

Figure 3: Do you see any difference in terms of percentage between ivermectin and permethrin by age group? If so, you could also describe and discuss it.

I think would be also nice to add an additional figure showing the trend of incidence per age-group during the study period using the data reported in table 2, supplementary material.

**********

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Reviewer #1: Yes: Zaida Herrador

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PLoS One. 2022 Jun 24;17(6):e0268865. doi: 10.1371/journal.pone.0268865.r002

Author response to Decision Letter 0


25 Apr 2022

Response to reviewers

We would like to thank the reviewers for their time and comments on our manuscript. They were really helpful and valuable for improving our manuscript. Below we give a point-by-point response to the reviewers.

Reviewer #1:

General comment

Overall, even if the topic is quite relevant, the paper is quite poor. The intro and methods sections need to be improven and completed.

Abstract

The main objective is too ambitious, a research shouldn´t be triggered by an assumption, please rephrase. We adjusted the aim of the study, see line 20 and 59.

Introduction

Overall, the introduction is quite short. I would recommend to add a short description on disease background, not only on clinics and current challenges (i.e. treatment resistances) but also on its worldwide epidemiology (including the fact that it´s an NTD). Great suggestion, we added some additional information on disease background, epidemiology and treatment. See lines 40 and 49.

Line 36: Is it possible to sustain this information (“general practitioners (GPs) observed a gradual increase of scabies diagnoses in 37 the Netherlands”) with some references? It is partly based on the presented incidence number in our study; however, it was never published in a manuscript before. So therefore, we cannot sustain it with references.

Line 40: Are the PHS notified of individuals attending this kind of vulnerable setting? Or are you referring to aggregate/outbreak data? Please specify. We clarified in the text, see line 48.

Line 46: same comment that above. The main objective is too ambitious, a research question cannot be based in previous assumptions. We adjusted the aim of the study, see line 59.

Methods

Line 55: Would it be possible to include some information of population coverage?

Is there any other available data source to understand the situation on institutionalized residents? Why the authors did not analyze the information notified to the PHS on vulnerable settings? We clarified in the discussion, see line 208.

Which was the study period for this first data source? Does it gather info also from private clinics? We clarified in the text, see line 72and 74.

Line 58. Please describe in detail which sort of descriptive analysis was performed. Results by sex are also given in the results section, but this is not explained in methods. We clarified in the text, see lines 75 and 88.

Line 67. Are these treatments only used for scabies? Please specify. We clarified in the text, see lines 87.

Further spatial analysis could have been performed based on the pharma data. We don’t have data on the location of the dispensations, so therefore spatial analysis could not have been performed.

Ethical statement: There is a reference to outbreak investigations, but this information is not included in the analysis, is this correct? That is correct, thank you for noticing. We adjusted our ethical statement, see lines 95.

Results

This section is a bit poor. A table with some additional data is recommended. Was the study period the same? Did you find any temporal relationship between both databases? A bit more advanced analytical techniques (such as linear regression, joint point analysis) could help to better assess the temporal trend of this disease. Great suggestion, we calculated a correlation coefficient to describe the correlation between the incidence of diagnoses and the number of dispensations between 2011 and 2020, see lines 65 and 130.

Line 87. This last sentence should be placed in the discussion section, as it´s not referring to study results. Thank you, we removed it from results section.

Line 105-108: this belong to the discussion section. We removed it to discussion section, see lines 157 – 159.

Discussion

Line 124. This first statement cannot be based on the provided results (due to the limitations of both data sources). We added the word ‘ reported’, since is it not an notifiable disease and thus dependent on patients who consult the GPs, see line 151.

Line 131. It is probable that the incidence of notifiable diseases has decreased during the COVID-pandemic, but also there might have been underreporting. Regarding scabies, and given its transmission mode (which should be better explained in the introduction section), the impact of the COVID pandemic might be the opposite (somehow, homes became close institutions). Also, the high burden on GPs might have also affect the attendance and follow-up of patients, worsen the situation. Great suggestion, we’ve added it to the discussion, see line 162.

Line 139. What is the relationship between population growth and increase in scabies incidence? Is this related to worst health conditions and poverty? Thank you for noticing, it was in the wrong place and is now replaced in line 176.

Regarding the increasing trend in young population, is it possible that sexual transmission of scabies has also increased? Great suggestion, it is possible since it is transmissible by prolonged skin-to-skin contact. We mention sleepovers as well in our discussion, see line 165.

Line 154. I don´t think this is an explanation of COVID times, on the contrary, incidence should have decreased. We rephrased the paragraph, see lines 182 -192.

Line 157. This paragraph does not discuss the study results. Please rephrase or delete. We integrated with another paragraph in our discussion, see lines 223 – 233.

Line 163. Even if you don´t have info on resistance, an increase in other treatments rather than permethrin could had supported this hypothesis. Interesting suggestion, however as we don’t have any information on re-infestations, failed treatment and indication for the prescription, we cannot claim that the increase in other scabicides can be explained by resistance.

Line 180. You may add a reference to EMA recommendations against the use of ivermectin for COVID-19 EMA advises against use of ivermectin for the prevention or treatment of COVID-19 outside randomised clinical trials | European Medicines Agency (europa.eu). Thank you for the reference, we included it in the discussion.

Line 197. Looking at the incresaing number of cases, would you also recommend better training, medical guidelines, etc for primary health care centres? Great suggestion, we added it in line 242.

Reviewer #2:

The authors present an increasing incidence of scabies infestations in the Netherlands during 2011 – 2021. The manuscript confirms what previously reported by other countries in Europe, as well as providing additional information during more recent years under the pandemic context. The manuscript is interesting and deserve to be published, here below some points that could improve clarity and the quality of the manuscript.

Language revision, preferably by a native speaker, would improve the quality of the manuscript. For example, the use of the word ‘several’ would fit better than ‘multiple’ in some sentences. In the title ‘scabies diagnoses by general practitioners’, I would add the word ‘reported’ before ‘by’. Similarly for the title, ‘Scabicides prescriptions and over-the counter sales by public pharmacies’, I would add ‘reported’ or ‘recorded’. Line 150, I would replace ‘since’ with ‘in’. Thank you for your suggestions, we revised our manuscript following your comments.

Introduction, line 44, I think the sentence ‘There are complexities concerning scabies surveillance: clinical recognition and diagnostic tools such as microscopy, dermatoscopy and PCR have sensitivity issues’ is a bit out of place since it is not a notifiable disease in the Netherlands, and does not connect well the sentences before and after. It could be deleted from here and be used in the discussion part when relevant. We removed the sentence, it will be discussed in the discussion, see lines 223 – 233.

Methods part, line 52, it is mentioned ‘2011-2020’ while in the introduction and abstract it is mentioned 2011-2021 period. This is confusing to the reader. My understanding is that the data on scabies diagnosis was available until 2020. If this is the case, authors should clarify somewhere in the manuscript the reason why data from 2021 were not included. This is correct, thank you for highlighting. We added some information on why we could not include the incidence of 2021 in our study, see lines 78 and 207.

Methods part, line 68, could you specify more in details the type of treatment? E.g., permethrin cream? Ivermectin tablets? Is It possible to add in introduction which treatments are used in the Netherlands? We added some information on treatment in the introduction, see line 49.

Ethical statement, line 73, the authors stated, ‘outbreak investigations of notifiable diseases such as scabies’ while in line 38 ‘cases of scabies are not notifiable’. I would suggest rephrasing to make it more understandable what you mean in the ‘ethical statement’ section. Thank you for noticing, we adjusted the ethical statement, see line 95.

Results, line 87, ‘Remarkably, this was despite the COVID-19 pandemic and its corresponding control and hygiene measures.’ I think it is a very interesting results, do you have any hypothesis on this aspect? Could you add a sentence or short paragraph in discussion section providing an explanation/hypothesis of this phenomenon based on your experience? We have included our hypothesis in the discussion, see lines 165 – 168.

Results, line 83, ‘No differences were observed between men and women.’ while line 97 ‘Slightly more males bought a scabicide then women’. Is there a possible explanation for this difference? Great question. We don’t have a distinct explanation for this difference, however, Germany observed that more males were diagnosed with scabies. We added this in the discussion, see lines 185 -188.

Do data on scabies diagnosis include recurrent cases (re-infestation) or it was possible to identify records from the same patient in your dataset? This need to be clarified and added as limitation if was not possible to look at re-occurrent cases. This is mentioned as a limitation in the discussion, see lines 211-215.

It is mentioned in line 59 ‘Most institutionalised residents are not taken into consideration in these registrations, considering other physicians are usually responsible for their consultations.’ What about the database on pharmaceutical data, does it exclude as well the treatment of institutionalized residents? If not, this need to be clarified and/or added as limitation. We clarified in the text, see lines 205 and 206.

Line 180 ‘ivermectin could also be prescribed as a drug against COVID-19, while it is proven not to be effective (15). This can explain the sudden rise of ivermectin dispensations at the end of 2021.’ Including data on scabies diagnosis in 2021 would allow to have more solid conclusion. If you did not compare it with scabies diagnosis data, I would amend ‘this can explain’ with ‘this could explain’. We rephrased the text, see lines 221.

Line 183 and line 193, the authors mention ‘surveillance’ but it is not a notifiable disease, could you clarify and rephrase it if needed? We rephrased the text, see lines 224 and 238.

Figure 1: Did you try to compare the incidences level reported in the Netherlands with the ones reported in other countries? Anything to highlight? A sentence/paragraph on this aspect can be added in the discussion providing authors’ perspective. We compare the trends in incidence and in dispensations of other countries in the discussion, see lines 172-180.

Figure 2: does the 3-months average add something to the interpretation of results or discussion. If not, I would simplify it deleting them for permethrin and ivermectin. Thank you for your suggestion, we removed the 3-moths average, see the revised figure 2.

I would also integrate figure 1 with figure 2, visually comparing the two datasets on scabies diagnosis and dispensations of scabicides. You could also use number of diagnoses instead of incidence, if this will improve the data visualization. The values on incidence per year are available in supplementary material in any case.

Great suggestion, however, the incidence data is only available per year which would be hard to read if you overlap both figures. The pharmaceutical data is relevant by month because of the seasonality. Furthermore, we now calculate the correlation coefficient to describe the correlation between the incidence of diagnoses and the number of dispensations between 2011 and 2020. Therefore, we decided not to integrate figure 1 and 2.

Figure 3: Do you see any difference in terms of percentage between ivermectin and permethrin by age group? If so, you could also describe and discuss it. We included it in the results section, see line 138.

I think would be also nice to add an additional figure showing the trend of incidence per age-group during the study period using the data reported in table 2, supplementary material. Great suggestion, however, when the number of dispensations by age group per month is plotted, it gives the same trend as seen in Figure 2 which will not give any added value visually. We mention it in the results, see line 139.

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Decision Letter 1

Joël Mossong

10 May 2022

Increasing incidence of reported scabies infestations in the Netherlands, 2011 – 2021

PONE-D-22-04888R1

Dear Dr. van Deursen,

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

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Reviewer #2: No

Acceptance letter

Joël Mossong

6 Jun 2022

PONE-D-22-04888R1

Increasing incidence of reported scabies infestations in the Netherlands, 2011 – 2021

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