Nasopharyngeal Staphylococcus aureus colonization among HIV-infected children in Addis Ababa, Ethiopia: antimicrobial susceptibility pattern and association with Streptococcus pneumoniae colonization

  1. Henok Alemu Gebre
  2. Ashenafi Alemu Wami
  3. Eyerusalem Solomon Kebede
  4. Melaku Yidnekachew
  5. Meseret Gebre
  6. Abel Abera Negash

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Abstract

Background. Staphylococcus aureus and Streptococcus pneumoniae are common inhabitants of the nasopharynx of children. HIV-infected children have higher risk of invasive diseases caused by these pathogens. With widespread use of pneumococcal conjugate vaccines and the emergence of methicillin-resistant S. aureus , the interaction between S. aureus and S. pneumoniae is of a particular significance. We sought to determine the magnitude of colonization by methicillin-sensitive and -resistant S. aureus and colonization by S. pneumoniae ; associated risk factors and antimicrobial susceptibility pattern among HIV-infected children in Addis Ababa, Ethiopia.

Method. A prospective observational study was conducted among 183 HIV-infected children at ALERT hospital Addis Ababa, Ethiopia from September 2016 to August 2018. S. aureus and S. pneumoniae were identified using standard bacteriological techniques, antimicrobial susceptibility testing was performed on S. aureus and screening for methicillin resistance was carried out by amplifying the mecA gene. Risk factors were analysed by using binary logistic regression.

Results. The prevalence of nasopharyngeal S. aureus , MRSA and S. pneumoniae colonization were 27.3, 2.7 and 43.2 %, respectively. Multivariable analysis indicated an inverse association between S. aureus and S. pneumoniae nasopharyngeal colonization [aOR, 0.49; CI, (0.24, 0.99); P=0.046 ]. The highest level of resistance in both methicillin-sensitive S. aureus (MSSA) and MRSA was observed against tetracycline.

Conclusions . We found an inverse association between S. aureus and S. pneumoniae colonization among HIV-infected children. Continued assessment of the impact of pneumococcal conjugate vaccines and antiretroviral therapy on nasopharyngeal bacterial ecology is warranted.

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  1. Version published to 10.1099/acmi.0.000557.v3 on Access Microbiology
  2. Access Microbiology

    Thank you for addressing reviewer comments. However there are still some calculation errors in the manuscript- please check all % calculations again before the manuscript goes through final processing.

  3. Access Microbiology

    Comments to Author

    The authors have addressed concerns in first review, and the results are now well situated within the relevant literature. Minor comments Table 1 male 90/183 is given at 72.2%. Please re-check all percentage calculations very carefully. spelling pharyngeal on line 109 remove apostrophe from prevalences line 271

    Please rate the manuscript for methodological rigour

    Good

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

    Satisfactory

    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

  4. Version published to 10.1099/acmi.0.000557.v2 on Access Microbiology
  5. Access Microbiology

    Please address the reviewers comments below, paying particular attention the the data presented in table 1 as the data given for % colonised with S. aureus appear to be incorrect.

  6. Access Microbiology

    Comments to Author

    This manuscript describes the investigation of the nasopharyngeal carriage rates of Staphylococcus aureus in HIV infected children attending All Africa Leprosy Rehabilitation and Training Hospital (ALERT) paediatric HIV clinic in Addis Ababa, Ethiopia. The magnitude of colonization by methicillin-sensitive and -resistant S. aureus and Streptococcus pneumoniae and the associated risk factors and S. aureus antimicrobial susceptibility pattern 5-6 years after the introduction of the pneumococcal conjugate vaccine (PCV10) in Ethiopia were also investigated. There is a lack of data on the colonisation rates in this population and therefore this study provides valuable information to the field. There are however, some points for the authors to consider/address in order to improve the presentation of their findings in this manuscript. 1. Line 74- Should 4-fould be amended to 4-fold? 2. The data presented in Table 1 is difficult to interpret. a. What is the denominator in the "Colonized with S. aureus" column? b. Please explain what the percentages (%) in the "Colonized with S. aureus" column refer to. 3. Table 1 appears to correctly list the percentage of pneumococcal colonisation as 43.2% (79/183) however, line 234 lists the percentage as 43.3%. Please explain the reason for this? 4. Table 2. The legend does not include the definition for cOR. 5. Lines 247-253 - What are the values (numerators and denominators) used to calculate these percentages? 6. Line 255 - Repeated use of the word "of". 7. Line 263 - please clarify that this reported prevalence was observed in the study cohort and not necessarily the entire population of Ethiopia. 8. Lines 267-268 - Suggestion to expand on the differences noted. For example, the increased vs decreased used of antiretroviral drugs, what types of PCV vaccine were used and the vaccine uptake rates. 9. Line 291-294 - Are you implying that "HIV-uninfected" children have reduced mucosal immunity compared to those infected with HIV? I am not sure that this is what the referenced publication is stating. Please can you clarify this statement. 10. Please include the range of the CD4+ T cell counts observed in the study participants. 11. Line 307 - Although not presented in this manuscript, is there a correlation between the CD4+ T cell counts and the carriage rates in this study cohort to support this theory? If so it would be useful to include these findings. 12. Line 318 - "since we sampled only sampled nasopharyngeal swabs" please clarify this sentence. 13. Lines 319-320 - "the results might be fully representative of children in the whole of Addis Ababa or Ethiopia" why does this study cohort fully represent the children in the whole of Addis Ababa or Ethiopia? 14. Line 328 - Do you mean the nasopharyngeal colonisation rates of S. aureus or total colonisation based on all the bacteria isolated in this study. 15. Please include a description on how the MSSA, MRSA and pneumococcal carriage rates observed in the HIV infected children in this study compare to those reported in studies of HIV-uninfected children in Ethiopia and similar populations.

    Please rate the manuscript for methodological rigour

    Satisfactory

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

    Poor

    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

  7. Access Microbiology

    Comments to Author

    1. Methodological rigour, reproducibility and availability of underlying data This is an observational cohort of HIV infected children, reviewing frequency of colonisation of MSSA, MRSA and S. pneumoniae. The authors aim to report prevalence in HIV infected children in the post PCV period, and the study design chosen is appropriate to this aim. Study is conducted with well described methods. In Methods, sample size paragraph implies this was designed to provide a comparison to another observational study of S. aureus nasal carriage in Uganda post PCV rollout. If designed as a comparison so, this should be made explicit and results presented. However if no comparison is being made, this sample size calculation can be omitted. Associated clinical details collected, giving a thorough list of possible RF. Authors should include a description as to how missing data is handled? Microbiological methods are appropriate and ethical concerns given due concern and adequately addressed. 2. Presentation of results Table 1 - Reason for hospital visit appears to have missing data; please ensure all missing data is clear (eg state for how many the observation is not available Table 1 - % figures given for various observations in those with S. aureus appear to be incorrect. eg S.pneumo carraige 15/50 Yes, but % given is 21%, and 35/50 given as no, % given is 28.4 (should be 70%) LRTI in last 3 months 2 of 50 answer yes, % given is 1.6%; 48/50 answer given is now, % given is 48.4 Please review all % calculations in this table - this is the major revision required, and without being certain that the numbers provided are accurate, can't state that the conclusions are supported by data Please also add the total number to the top row for "Colonised with S. aureus" to make this clear In presenting data on antimicrobial susceptibility, care needed with the term 'level', which is often used to refer to the MIC compared with cut off (eg 'high level gentamicin resistance' in Enterococci). For avoidance of confusion, suggest use of 'rate' when describing the proportion of isolates with observed resistance. Please provide a definition for MDR in this context 3. How the style and organisation of the paper communicates and represents key findings Clear tables present the observations clearly and there is a good flow of findings and discussion 4. Literature analysis or discussion A key prior publication of this problem in this setting is not mentioned in the discussion (where a lack of prior information is cited as a motivating factor for the study - line 109), but is cited in discussion as a comparison (line 264). While the existence of prior work does not negate the value of this, it's hard to reconcile those two statements. I would encourage the authors instead to acknowledge this prior literature in the introduction and use the discussion to make clear the additional or contrary results provided by this study (as they do regarding MRSA) The discussion on different observations between S. aureus and S. penumoniae in children living with HIV with and without ART is informative and clear 5. Any other relevant comments The authors could consider including in discussion what they see as the clinical implications of these findings. Minor comments - lines 67-68 rephrasing to the 1960's (or replace with 1961); and I understand CA-MRSA reported as early as the 1980s David MZ, Daum RS. Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev. 2010 Jul;23(3):616-87. doi: 10.1128/CMR.00081-09. PMID: 20610826; PMCID: PMC2901661. - line 72 - cited reference 5 does not appear to establish the claim that HIV increases risk of S. aureus infection

    Please rate the manuscript for methodological rigour

    Good

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

    Good

    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

  8. Version published to 10.1099/acmi.0.000557.v1 on Access Microbiology