Author’s response to reviews Title: Human metapneumovirus prevalence and patterns of subgroup persistence identified through surveillance of pediatric pneumonia hospital admissions in coastal Kenya, 2007-2016 Authors:

1. Line 34: The part you described about the prevalence of HMPV among all samples tested, you can just use 1 decimal place like other parts in the paper. Our Response: We have changed this to 4.1% and not 4.10% (line 34). Materials and Methods 2.Line 92-93: for the inclusion criteria, it is mentioned that those children with either severe or very severe pneumonia were enrolled in the study. Did you also do HMPV screening test for those with ARI hospitalized children without pneumonia symptom? If so, it might be good to put those data in supplementary data as it might be an interest for some readers. It might be better if you could include the definition for hospitalization in this hospital setting as well. Our Response: Cases were defined as patients presenting with syndromic pneumonia (severe or very severe), and only cases were tested for HMPV. Controls (children without syndromic pneumonia) were not tested. The reviewer is referred to a previous study by (Owor et al. 2016) who has reported HMPV occurrence in both cases and control, in this same hospital. For admission or hospitalization criteria, the clinician recommends hospitalisation upon review at the time of patient presentation, for instance, if the child has the above-mentioned pneumonia symptoms, they will be admitted. We have included this definition in the Materials and Methods section (line 90). 3.Line 90-93: You stated that you collected throat swabs, nasal aspirates and washes, or sputum specimen. Is it consistent in terms of type of samples being collected from each study participant? For example, it may be technically difficult to collect nasal aspirate / wash or sputum from younger children compared to adult participants. Ideally, the type of samples collected should be nearly identical among all age groups. Our Response: Sputum samples were not part of the study. It is true that over the time period of this study there have been changes to the collection procedures. However, we would argue there is some consistency in our collection method in that all sample involved collection of material from the deep nasopharynx. Our staff are well trained and experienced in collecting samples from all ages and we do not believe the patient age to be an issue in terms of sample quality. We have revised the sentence to clarify sample collection methods ( line 97-99). 4.Line 95-96: For the sample collection, it was described that nasal wash, NP, or NP/OP were collected from enrolled cases. in terms of the samples used for the HMPV screening step, was it consistent throughout the current study period? Our Response: We used all the sample types mentioned. Samples from different sites may favour collection of one pathogen over another (eg Hammitt et al, 2011 ). However, as stated above the consistent aspect is that all include a sample from the deep nasopharynx. 5. Line 100-111: For the HMPV screening as well as nucleic acids extraction methods used in different study period, did you verify that detection sensitivity etc. do not statistically vary among different kit? Our Response: Provisional (unpublished) comparison data from our studies show that the different extraction methods used vary insignificantly in the rRT-PCR cycle threshold (Ct) values. For instance, Ct values from the Viral RNA Mini kit (QIAgen, Germany) method are 0.75 fold higher than QIAcube HT kit (QIAgen, Germany). 6. Line 162 and 246: I feel rather comfortable to use the term "genotype shift" over "genotype change" since "genotype change" may probably mean that a certain genotype (that already exists) change to another genotype, which is wrong in this context. Our Response: The authors appreciate the reviewer concerns. In the manuscript, we implied change of observable genotype prevalence or predominance and have made this clarification in the revised manuscript (lines 168 and 183). We prefer not to use “genotype shift” as it has other associated connotations such as antigenic shift. 7.Line 163-164: could you justify the reason why use chi-squared test for the clinical severity comparison among different HMPV genotypes? As shown in the table 3, the value of some cells are less than 10; for example, (n=2) in A2c (very severe) and (n=10) in B2. In this case, the result of chi-square test may not reliable as the one from fisher's exact test. Results Our Response: Thank you. This was in error; the reported results were for Fisher’s exact test (line 42 and 352). We have corrected this (lines 42,170). 8. Line 172-173: it was described that clinical samples were successfully collected only from 74% of those study enrolled patients. It is considerably high and needs to be mentioned in discussion section. Also, it may be necessary to state that those samples-collected group and group without clinical sample are not significantly different in terms of characteristics if that is the case. Our Response: The reviewer raises a good point. The pneumonia surveillance study aims to recruit all eligibles. We failed to collect from 24% of the eligibles in this study. We have previously reported similar results, which results from refusals and difficulty in collecting from the most severe cases (Nokes et al, 2009). Hence, we cannot argue that the clinical component of the cases for whom samples were collected is no different from those whose samples were collected. Hence, if some HMPV variants are associated with disease severity there may be a bias in the resultant composition in our study. However, the proportion not collected shows no systematic change over time and so it seems unlikely any bias in the prevalence of HMPV groups, genotypes and clusters have changed over time. We have mentioned this in the manuscript (line 344-352). 9. Figure 1: in figure legend, it might be informative if you could put which bootstrap value was used as cut-off. For example, those bootstrap value higher than 70 was considered to be significant etc. Same for other ML-based phylogenetic analysis. Our Response: We have included the the bootstrap values in all trees and mentioned the cut-off in the figure legends. 10.Figure 4: I understand that cluster unique amino acid substitutions were presented in figure 5, it might be also informative to put some of those information at the branches of Figure 4 if this will not make the trees too complicated. In that way, it might be easier for readers to visually understand the uniqueness of each genetic cluster. Our Response: Done. We have used same variant Id.s used in figure5 (now, supplementary figure2 and 3) to label the different variants along the branches in the revised figure 6. 11.Line 217-220 & Line 232-235: have you tried to statistically compare the difference in evolutionary rates among different genotypes? If this is your interest, you can easily compare using such as Welch's test, in which it assume two groups in comparison have normal distribution, yet the standard deviation may differ between two. In case of comparison among more than two groups, it might be worth using Kruskal Wallis test for testing null-hypothesis. Our Response: Kruskal test may not be suitable for the comparison of the differences in Evolutionary rates between the groups. Instead we used highest posterior density intervals (HPD), if they overlap the difference is not significant.