PONE-D-21-40227IMPACT OF UNIVERSAL VARICELLA VACCINATION ON THE USE AND COST OF ANTIBIOTICS AND ANTIVIRALS FOR VARICELLA MANAGEMENT IN THE UNITED STATESPLOS ONE

Dear Dr. Pawaskar,

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Additional Editor Comments (if provided):

Dear Dr Pawaskar and colleagues,

Your manuscript has been reviewed by two experts in the field. Both reviewers and I agree that your manuscript is well written and of interest to the field. Minor revisions are requested to improve the manuscript, please do so per reviewers' suggestions.

Best regards,

Georges MGM Verjans

www.herpeslab.nl

Dept. Viroscience

Rotterdam

The Netherlands

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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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: This manuscript presents a version of a cost-benefit analysis for varicella vaccination in the United States in 2017. The authors show the expected cost reductions associated with universal vaccination in the USA. The goal of the report appears to be an opportunity to convince other countries to authorize universal varicella vaccination. A few comments are listed below.

1. Results, Varicella cases, lines 124-8 and Table 1. This table contains numbers that are not widely known among vaccine experts. The authors state that 93.8% of children in the USA were vaccinated against varicella in 2017. Yet the authors estimate that 396,633 cases of wild-type varicella (chickenpox) occurred in the remaining unvaccinated population of children. Please write more in the text about how the authors arrived at the number of 396,633. Furthermore, the authors estimate that 140,395 cases of break-through varicella occurred in the fully vaccinated children. Please write more in the text about how the authors arrived at the number of 140,395.

2. Add new section near the top of the Discussion about varicella herd immunity. If the number of cases of varicella in Table 1 are correct, the USA does not appear to have achieved herd immunity for varicella, even with an immunization rate of 93.8%. This is a striking conclusion, especially when we are at the end of the COVID-19 epidemic. In the USA, about 65% of the population has received complete COVID-19 vaccination. Can the authors state whether they think varicella or COVID-19 is more contagious? If they are roughly equally contagious, based on this report, the USA will never achieve herd immunity against COVID-19 by immunization, since we will never achieve greater than 92% COVID-19 vaccination. After the COVID-19 epidemic, there appears to be ever greater resistance to vaccination in the USA. Please discuss the above points in a new paragraph in the Discussion about what is meant by herd immunity and whether we have achieved herd immunity to varicella in the USA in 2017?.

3. Abstract. Suggest that one sentence about herd immunity be added into the Abstract. Was there herd immunity in the USA in 2017 against wild type varicella? Presumably herd immunity would never be achievable with an 80% immunization rate?

Reviewer #2: The aim of this study was to estimate the use of antivirals and antibiotics for treating varicella in children. The impact of vaccination was modeled after the experience in the U.S., where Varivax coverage is high. The use of antimicrobial therapy was estimated from a prescriber survey of 8 clinical vignettes. The parameters of the model were taken from published sources, although the actual reported varicella cases from the CDC were not used. This model was also used to predict the cost savings from reduced prescriptions in countries where vaccine coverage was absent, intermediate, or high. The findings presented here are interesting and compelling, although they should be taken as estimates only. These results could be used for future policy decisions on implementing varicella vaccine guidelines.

Line 127: correct typo, remove “were”.

Line 149: correct typo “d”.

Line 225: correct typo “nay”.

Supplemental Table 6 contains the key estimates of the model. However, it is difficult to find the “Total Varicella Cases” and the “Total Cases with no complications” and further down the “Total Cases with complications”. These rows are shaded gray and the font is bold. Why are these values not the top rows of the entire table? Why are they embedded in other rows that show the number of cases treated with antivirals or antibiotics? Every other row is a subset of these two key estimates, which form the base cases from the model.

In the Discussion, the point is raised that the estimate of total varicella cases may be high compared to the CDC estimates. How much higher? The CDC estimate should be included here, and the justification not to use that value should be explained. In fact, herd immunity will have a strong effect on the actual number of varicella cases in the U.S., because outbreaks of chicken pox are becoming rare. More often, varicella arises in unvaccinated children (or infants <1) who are exposed to adults with zoster. A more nuanced discussion of this situation could be added to the manuscript.

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Reviewer #1: No

Reviewer #2: No

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IMPACT OF UNIVERSAL VARICELLA VACCINATION ON THE USE AND COST OF ANTIBIOTICS AND ANTIVIRALS FOR VARICELLA MANAGEMENT IN THE UNITED STATES

PONE-D-21-40227R1

Dear Dr. Pawaskar,

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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Kind regards,

Georges M.G.M. Verjans, MSc, PhD

Academic Editor

PLOS ONE