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Posted by whiteroseupton on 23 Feb 2018 at 17:56 GMT

Dear Prof/Dr Carmen Munoz-Almagro

I write to please ask you for additional information to help my colleagues and I interpret the data reported in your interesting manuscript in PLOS one.

1. Please could you advise whether blood samples used for MBL genotyping were collected at the time of admission to hospital with pneumococcal infection, or were these obtained later? (Presumably later, otherwise you might have had genotype information available for the children who unfortunately died).

2. In the first line of your methods section, you report that 104 PM episodes were identified among 93 children. This implies that one or more children experienced more than one episode. It is not entirely clear whether you subsequently used number of episodes, or number of children, for your results. In the results text, sometimes the denominator is 93 children (eg, 29/93), and sometimes 104 episodes (eg 12/104, 33/104 and 8/104 excluded for various reasons). Therefore it is not entirely clear whether the overall denominator used to analyses results, N=48, refers to children, or episodes. If episodes, please could you advise whether any child was counted more than once?

3. Please could you explain how many of the 8 children who died were aged < 12/12. (The paper reports the number aged <2 years, even though your analysis divided children into those aged <12/12 or >12/12)

4. Please could you explain why you divided children into those <12/12/>12/12, when the second paragraph of your introduction, and the second paragraph of your discussion refers to <2 years of age as being relevant to colonisation by low invasive capacity serotypes, and to the role of the innate immune response. Was a cut-off at 12/12 a post-hoc or an a priori decision?

5. I would be grateful if you could comment on the implications of missing data for the children who died. (Are there any published data from other groups, or from your own, about the relationship between death from IPD or PM and MBL2 deficient genotype?)

Thank you in anticipation of your help

Yours sincerely
Dr M. Upton MBBS MRCGP

Competing interests declared: I am one of 4 students at the University of Birmingham, UK, undergoing postgraduate training in medical genomics, who are studying your manuscript for our course-work.
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