PONE-D-22-30455The prevalence, clinical characterization, and seasonal trends of enteric pathogens among patients with acute community-acquired diarrhea in North LebanonPLOS ONE

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: The manuscript of Osman et al describes a very well designed epidemiological study of the etiology of community acquired acute diarrhea in North Lebanon. The work enrolled 360 patients of different ages and included evaluations of clinical outcomes and risk factors. The data obtained is of high interest not only for the Lebanese health system but also for the researchers in the field. The authors found a high frequency of diarrheagenic Escherichia coli pathotypes, specifically EAEC and EPEC, and rotavirus A. The data is adequately presented and analysed, including multivariable logistic regression analyses. A large number of mixed infections was detected and the composition of them is presented. This could be highlighted in the discussion section in the view of the severity or associated clinical symptoms of these case. Also, two other limitations of the study should be considered in the discussion: the wide range of the patients ages (1-91 years old) and the lack of EPEC and EAEC sub-typing (typical and atypical isolates).

Minor points:

- page 4, 2nd paragraph: Important studies from the group of Richard Guerrant conducted in Fortaleza, Brazil, should be cited to support the information regarding the impaired cognitive consequences of diarrhea in children leaving in low income areas.

- page 5, lines 19-25: The text fragment starting as "For example, 11% of hospitalized...", finishing as "acute gastroenteritis, respectively [31]", would be more appropriate in the Discussion section.

- page 6: What does WASH stand for?

- Figure 2: Rearrange the bars in descending order of prevalence.

- Figure 3B: Not all types of co-infections detected are represented. This part of Fig. 3 could be presented as Supplementary Material describing the composition (enteric pathogens) found in all mixed infections. This is a relevant result to be presented.

- Figure 3B: Detection of co-infections is a common finding in epidemiological studies of the etiology of acute diarrhea in low income countries. However, co-infections of 4 enteric pathogens such as the one presented here (EPEC, EAEC, ETEC and EIEC) is notable, if real. Did the authors investigated the accuracy of such infections in 6 patients? Fecal culture and further colony identification? Separate PCR detection?

- page 14, line 12: Please change the reference 55 for other relevant references to support the point discussed regarding the pathogenesis of EAEC. Several reviews on EAEC pathogenesis would fit better here.

- page 14, line 16: The authors could discusses here the lack of sensitivity when using serum agglutination detection the so-called classical EPEC O serogroups.

Reviewer #2: Osman et al.

In this work that authors used robust molecular diagnostic methods that target multiple etiologic agents increases the sensitivity and specificity of detection for most enteric pathogens. To better understand the epidemiology of enteric infections, they aimed to determine the prevalence of enteric pathogens, identify risk factors and seasonal variations, and describe associations between pathogens among diarrheic patients in a Lebanese community. The authors found a high prevalence of enteric pathogens, with a predominance of mixed infections. Their statistical models revealed a strong relationship between different diarrheagenic Escherichia coli. Rotavirus A was significantly more likely to occur in the winter season in comparison to the summer. Furthermore, they found that living in rural areas and swimming are considered significant risk factors associated with rotavirus A and norovirus GI/GII infections, respectively. It is a very interesting and well-designed study and the authors’ conclusions are supported by their evidence. I have only minor concerns:

1) Discussion section, third paragraph: EPEC does not cause dysentery.

2) In fact, the reference 56 does not mention the word “dysentery”.

3) Discussion section, third paragraph, penultimate sentence: rewrite that sentence so as not to give the impression that the authors' work includes bacterial resistance experiments (clearly writing that this is a correlation with reference 57).

4) The conclusion section is too long and redundant, reduce it and try merging it with the conclusion as the last paragraph (or reduce the conclusion as well, it is redundant).

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Reviewer #1: No

Reviewer #2: No

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The indelible toll of enteric pathogens: Prevalence, clinical characterization, and seasonal trends in patients with acute community-acquired diarrhea in disenfranchised communities

PONE-D-22-30455R1

Dear Dr. Hamze,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Fernando Navarro-Garcia

Academic Editor

PLOS ONE

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