Epidemiology of Haemophilus influenzae in children on Lombok Island, Indonesia

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Abstract

The Haemophilus influenzae serotype b (Hib) conjugate vaccine routine immunization programme has been implemented for almost a decade; however, there is limited surveillance of H. influenzae carriage rates in the Indonesian population. H. influenzae was isolated from nasopharyngeal (NP) swab specimens of healthy children on Lombok Island, West Nusa Tenggara Province, Indonesia from 2018 to 2019. Serotyping was performed using quantitative polymerase chain reaction. We identified H. influenzae in 40 of the 96 (41.6 %) NP swab specimens. We identified 39 non-typeable H. influenzae (NTHi) isolates and 1 Hib isolate.

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  1. The revised version of this manuscript has largely addressed the concerns raised by reviewers. However, some issues remain with the revised version. There are still grammatical errors throughout the paper that need to be corrected. We offer a discounted translation service, Editage (https://www.editage.com/; see https://www.microbiologyresearch.org/prepare-an-article#13 for more information), if external assistance is needed. References 9, 11, and 13 are also missing information and improperly formatted. Please correct these concerns with the grammar and references.

  2. This study would be a valuable contribution to the existing literature. The reviewers have highlighted minor concerns with the work presented. Please ensure that you address their comments.

  3. Comments to Author

    This is a brief report of an H. influenzae carriage study on Lombok Island, Indonesia. The broader public health relevance of the study needs to be explained more clearly, and the estimate of the carriage prevalence should be given a 95% confidence interval. I have a number of other editing suggestions below. Comments 1. (Introduction) It would be helpful to give an explanation of why the prevalence of H. influenzae carriage on Lombok Island is of public health inter- est in the rest of Indonesia or beyond. Clearly, it is important on Lombok Island itself. But what do the findings mean for people who are not on Lombok Island? 2. (line 54) Instead of "which comprising", it might be better to say "which has" or "which contains". 3. (lines 77-79) From the description, it appears that the nasal swabs were taken from symptomatic children. If so, the estimated prevalence from this study would be much higher than a prevalence estimate based on a representative sample of children. 4. (line 79) The catch-up vaccination for children who became unwell needs more explanation. Was it a vaccination given to children in the control group who became unwell or did children in the vaccination group also receive an additional vaccination if they became sick? 5. (lines 79-82) The number of children in the original study should be specified. It is not clear what proportion of the children in the original cohort study is represented by the 96 children in the current study. The selection process for the 96 samples also needs to be explained because it affects the interpretation of the prevalence estimate. 6. (lines 91-93) The plural should be used: "All suspected H. influenzae colonies were confirmed . . . " 7. (lines 96-97) The first sentence of the Results & Discussion is not a complete sentence. It should say something like: "Ninety-six swab samples were collected . . . ". In the second sentence, it might be better to say "isolated" instead of "identified". 8. (lines 98-100) It might be better to say something like: "Based on polymerase chain reaction-based serotyping, 39 isolates were NTHi and only one was type b." 9. (line 100) The percentages male and female among positive cases should probably be calculated with the number of positive cases (40) as the denominator, not the entire sample (98). The current percentages show the proportion of the entire sample that are male positive cases and female positive cases, which does not seem to match the description in the text. 10. (lines 102-104) The comparison of the current study to the 1997 study seems to be comparing apples and oranges. The 41.6% carriage prevalence in the current study includes both type-b and NTHi, but the 1997 study seems to have found. 11. (Table 1) The n for each prevalence estimate is given in the fourth column, so it is not necessary to repeat it in the fifth column (e.g., "40/96"). These prevalence estimates should be given 95% confidence intervals wherever possible. In particular, the prevalence estimate from the current study needs to have a confidence interval. 12. (Table 1) It would help to arrange the rows in the table in decreasing chronological order (most recent at the top and oldest at the bottom). 13. (Discussion) The argument about the potential danger of invasive disease from NTHi is important, but it seems to be missing an important nuance. If vaccination has successfully controlled type-b H. influenzae, then it is not unexpected that some of this will be replaced by NTHi. The important public health question is whether the rate of invasive disease has gone up or down. The results of the present study do not answer this question.

    Please rate the manuscript for methodological rigour

    Satisfactory

    Please rate the quality of the presentation and structure of the manuscript

    Satisfactory

    To what extent are the conclusions supported by the data?

    Partially support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes

  4. Comments to Author

    Changing Epidemiology of Haemophilus influenzae carriage among Children in Lombok Island, Indonesia Reviewer Comments In present study, the prevalence of carrier H. influenzae in children was investigated to check the efficiency of implementation routine Hib immunization program in Indonesia. The article needs to add the following minor suggestions for further processing. * There are a couple of typographical, language and grammatical errors in the manuscript which need to be corrected. * increasing number of non-type b H. influenzae (NTHi)… The author has already defined the abbreviation so it is better to use abbreviation in the rest of article. * Reports showed that the rate of H. influenzae carriers is around 20% in infants and > 50% in children 5-6 years … Any possible reason for this? * Control and vaccine groups were age… Rephrase it. * pneumococcal vaccine (PCV)-vaccinated and control group…. Define the control group. * In the current study, we selected 96 archived… Which method was followed for selection of samples? * Suspect H. influenzae colonies were characterized…. Add reference. * serotyped utilizing a real time polymerase chain reaction… Add name of gens which were targeted for detection. * Add some lines in the last para of materials and methods that how the data was analyzed. * We also found that 69% of all the subjects…. Add detail about this questionnaire I materials and methods. * Add an image of PCR result which was used for detection of hpd gene for improving the paper. * Set the font size of references as per journal formate

    Please rate the manuscript for methodological rigour

    Good

    Please rate the quality of the presentation and structure of the manuscript

    Very good

    To what extent are the conclusions supported by the data?

    Strongly support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes