Immunization Status against Measles, Mumps, Rubella and Varicella in a Large Population of Internationally Adopted Children Referred to Meyer Children’s University Hospital from 2009 to 2018

Round 1

Reviewer 1 Report

The manuscript entitled "Immunization status against measles, mumps, rubella and varicella in a large population of internationally adopted children referred to Meyer Children University Hospital from 2009 to 2018" describes a 10-year Italian investigation of chidren adopted by Italian parents. It is a relevant and needed contribution. Below I include some suggestions to improve the clarity of the report.

Main points:

The introduction could be shortened and focused on the main topic. I believe that a detailed description of the measles elimination status in all European countries is not relevant, because the study is not about elimination of measles and does not have European coverage. I would therefore suggest introducing the Italian (tuscanian) vaccination programme and the adoption problem in italy and how this can influence herd immunity, with the emphasis of different herd immunity thresholds for different childhood communicable diseases. I would avoid judgmental generalisations that are not fully backed by data such as lesser effectiveness of vaccines in low-resource countries (line 61-62) or generalisation about how Chinese fake their vaccination certificates (lines 198-199). There is a bit too many illustrations, some having overlapping contents. I would suggest to remove Table 3 which is not adding a lot. Also the Table 6 presents apparently the same information as Figure 2 - the authors should select one of them.

Specific (minor) comments:

In the Table 3, the heading of the last column: should be "% of IAC from their respective continents" In the caption of Figure 2 and label of Y axis there is "antibody titre", while it looks more like a proportion of unprotected. In the methods, the authors did not mention measuring titres but classification as protected or unprotected... In line 180, the authors wanted to probably say that the written documentation did not reflect the immunsation status (and they wrote the opposite) In line 193-194, there is a text in Italian (looks the same as the following sentence in English). Typo in line 196: "African" not "Afrincan" Typo in line 207: "recruit" not "recruite"

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

Reemergence of Vaccine-Preventable Diseases (VPDs) is still threatening the global public health despite tremendous progress during the past decades. Small numbers of cases can lead to the re-emergence of VPDs if There are increasing numbers of unvaccinated people. In this manuscript, Bechini et al focus on immunization status of internationally adopted children that usually come from countries with poor healthcare resources.

Overall, I think this study was well designed and well conducted. A huge sample size was accumulated after 10-year continues research, which makes the data thorough and unbiased. The retrieved information is of interest and well presented and analyzed. The conclusions are also appropriate and informative, which may guide related organizations to pay attention on these people and improve the current vaccination policy.

There are only a few minor issues about language. For example, there are Italian in line 193 and 194.

Author Response

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Author Response File: Author Response.docx

Reviewer 3 Report

Thank you for your submission and interesting research. I have several comments for you consider:

Abstract:

Proper documentation of immunization is a worldwide problem (Vaccine 17 (2019) 5439-5451).  Maybe have last sentence of your abstract convey importance of serological testing for all age groups to verify seropositive results.  These viruses are extremely contagious and the reader may think it is only important in the groups you have selected (15-18 and those from Africa).  There is no information/chart of how many improper vaccine documentation were encountered when reviewing immunization records. Africa was one of the smallest groups at 347 so would be good to tie the number of improper documentation and serology of this group to understand why this statement was being made.

Introduction:

Line 45 -This may be a translation issue but it might read better if you delete "for a long time" and just leave it as "...the threshold to be reached and maintained to ensure herd immunity."

Line 55- References need to be cited in numeric order- should be 1,5 not 5,1

Methods & Materials

Study population Line 81- to avoid any ethical concerns I would add a statement that those not giving consent were excluded.

Line 86- I am not sure what was previously describe? Was this from another research project? If so, maybe add a supplement for the complete details. Maybe add that the electronic database was a secured system to protect patient information.

Line 92: Were the laboratory staff trained?  If so, please add that trained staff  performed the venipunctures.

Line 99- I am not sure why the age group of <1 was included since these vaccine would not typically be given to children under the age of one if they had one MMR for travel reasons they are still required to complete the two-dose series if given under the age of 1 and would not be given to children less than 6 months of age under any situation - it  is a total of 50 sub subjects in this category but muddies the data when including them in the serology data-they should be seronegative.

Line 106- A table of the number of doses documented would be helpful. Could break it down by country and repot number of 0 doses, 1 dose and 2 doses- could highlight the documentation problem with some records.

Results

Line 117- this sentence is a bit confusing.  Do you mean they were excluded because at least one serological test results was not available?

Line 121- Why did you not include mumps at 43.8% but all the other viruses?

Table 1- all the calculations are correct. Some suggestions for the table: Change America to Americas (have a key that explains includes North, Central and South America)

Also explain that the data from Russia is in Europe.  (Even though the most populated area of Russia is considered in Europe part of Russia is also considered part of Asia so it would clear to the reader).

Line 126- Have in the manuscript to refer to Tables 10 and 12 but there are no tables 10 and 12- Do you mean Tables 2 & 3?

Line 127- Should add percentages to numbers for consistency throughout the manuscript:

               Russia 458/1927 -23.8%

                Columbia 146/1927- 7.6%

               India 144/1927- 7.5%

               Ethiopia- 125/1927- 6%

Table 2- Fix America to read Americas since are including North, Central and South America

Table 3- Fix America to read Americas.  USA should be all capital letters currently is Usa.

Table 4- add % since are reported both i.e. Measles (n,%) not just “n”.  All calculations are correct.

Line 150- I am not sure why you included the data for less than 1 year of age they typically would not show antibodies unless they had the disease.  Age group 1-4 may have only received 1 dose and would not be fully protected.  I think this needs to be better explained for those that may not know the schedules of MMRV vaccines. Your data from ages 5 and up are more telling of immunizations missed.  There seems to be an emphasis on the under 1 and 1-4  age groups, that is skewing your data.

Line 159- It is expected that these age groups would not be protected since they are too young for the vaccine.  More focus should be o the age groups that should be protected abut are not.

Line 159-160 are bolded not sure why? Should they be bolded?

Discussion

Line 166- Reword this sentence it is unclear.  Are you trying to say this study has the largest number of subjects?  Might be just a translation issue.

Lines 193 & 194- These are in Italian- they need to be translated into English

I would be interested to see more of the documentation issues.  Was there a correlation with the antibody results?  There are a number of confounding elements (was the vaccine stored correctly etc..) to make a direct correlation difficult but it might have given you a sense if there was a particular area that seemed to have difficulties with documentation and serology. Maybe this is what you saw when identifying Africa with issues but the data was lacking in the manuscript.  What obstacles were identified when reviewing the immunization records?  Was it incorrect dates? Was the brand name of the vaccine documented but was recorded as not being an MMRV vaccine? Were there issue with translation of the immunization records?

Conclusions:

Could mention many factors influence vaccine status (low- income countries, lack of public health infrastructure) which why it is important to complete assessments in a timely manner to prevent outbreaks of VPDs.

References:

#9 should be correctly referenced as:

Centers for Disease Control and Prevention. CDC Yellow Book 2020: Health Information for International Travel. International Adoption. Avaible at:  web site  Accessed: insert date

Several grammatical and spelling issues in the manuscript need to be reviewed.

This is a topic that would be of interest to any healthcare provider that may encounter patients that recently adopted children from foreign countries.

Author Response

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Author Response File: Author Response.docx

Round 2

Reviewer 3 Report

Thank you for your revisions. 

A few comments:

Line 141- states older children were born in America.  Does this mean USA or South America (I am assuming South America since the previous paragraph identified Columbia as one of the most represented countries).  It might be best to clarify which part of the Americas this is representing (North, Central or South America) just for clarity.

Table 4 is labeled as Comparison between documentation recorded by the country of origin and the serological test performed in Italy- since there are no countries listed and the data is in aggregate may be consider renaming the table just comparison between documentation and serological test performed in Italy.

References:

Missing the number for the following references:  #10 and #15.  Reference #17 should be on a separate line and be numbered as #17.

I enjoyed reading the revised manuscript I think I highlights your work much better.

Author Response

Please see the attachment.

Author Response File: Author Response.docx