Phototherapy-Based Treatment for Sexually Transmitted Infections—Shining Light into Unexplored Territory

Round 1

Reviewer 1 Report

This review on the current and future potential uses of PT for STI agents is an interesting idea and one which would appeal to those in the field. However in its present form it lacks depth of information and requires more research into publications in this area. It misses out some important studies/findings, has a tendency to 'jump' from one area to another and needs more robust referencing.

To give some starting points for future versions:

Figures: There is a single figure in the manuscript (Figure 1) and I would suggest that this is checked through carefully - for instance - I am not sure why HPV is shown in Figure 1A as being located in the uterus but the cervix location is not indicated. Also where you refer to the figure in the text be  specific about whether you are signposting the reader to sections A,B or C.

Line 60 the authors start to discuss benign HPV conditions (which are caused by low risk HPV) and note various topical treatments followed up with physical treatment alternatives such as PT. This reads as if they are referring only to benign HPV conditions at this point. Line 67/68 then mentions therapeutic vaccines and notes they may be developed to prevent persistent HPV infection and HPV driven cancers. As cancers are high risk HPV type disease, and there has been no mention of malignant disease until this point, it seems out of place. See my comment about section 'PT for Viral STIs'

Line 69 states Gardasil can be used to prevent HPV. Why no mention of Cervarix or Gardasil 9?

Section PT for Viral STIs

Lines 136-138. The text states that '5-ALA-PDT can destroy warts and cause selective and specific destruction of sub-clinical virus infected areas' referring to Figure 1. The figure does not illustrate this at all. Ensure this figure is suitable for what you are trying to convey.

Line 173. "To explain encouraging results they .....etc." The authors need to expand on this statement otherwise the reader has to access the referenced study (REF 49) to see what the encouraging results are. More detail needed

Line 181 End of sentence reads "requiring additional". Text is missing and needs adding

Lines 214 -215 These appear at the end of a section about HSV but authors are discussing HPV so are out of place here and also repetitive as the information has been given before. Remove.

Importantly there is no mention or discussion of PT or PDT in high risk HPV disease (cancer). This must be addressed.

Line 279 PT for parasitic STIs. This section only discusses a single diagnostic PCR test for T. vaginalis. As this review is about treatments the study included is irrelevant. Would suggest the authors look at 

Silva Fonseca TH, Alacoque M, Silva Oliveira FM, Soares BM, Leite HV, Caliari MV, Gomes MA, Busatti H. Photodynamic therapy as a new approach to Trichomonas vaginalis inactivation. Photodiagnosis Photodyn Ther. 2018 Jun;22:91-95. doi: 10.1016/j.pdpdt.2018.02.006. Epub 2018 Feb 11. PMID: 29444462.

General Comment. References that have been cited are not always the most optimal. I suggest checking through all references and ensuring that citations are fit for purpose. The reference above for example should not have been missed.

Line 292 PDT for fungal STIs This section is overly brief and although there may be few patient studies on PT and fungal STIs there have been lab studies which should have been mentioned and other reports in a clinical setting such as Use of the Scar Acceleration Method - Mac in the Treatment of Vulvovaginal Candidiasis: A Proposal for Treatment in Public Health in Sus, Brazil. Marcus Vinícius de Mello Pinto et al Open Journal of Applied Sciences, Vol.10 No.11, 2020

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

1. Chemotherapy for Sexually Transmitted Infections has been also extensively investigated and tried in clinics. Comparison between chemotherapy and PDT for Sexually Transmitted Infections should be discussed and their advantages/disadvantages can be compared by Table.
2. I recommend that this review should contain "novel treatment technology for Sexually Transmitted Infections" such as nanoparticle/nanomedicine and immunological engineering.
3. In this review, authors preferentially discussed with 5-ALA but there are many kinds of 1st, 2nd and 3rd generation photosensitizers are available for clinical use. I recommend discuss with various types of photosensitizers for Sexually Transmitted Infections.
4.  Differentiation between simple phototherapy and photosensitizer-mediated PDT should be compared.
5. Provide Table(s) for the previously reported case of   photosensitizers/PDT wavelength/series of bacteria or virus.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

None

Author Response

The authors would like to take the opportunity to thank again the reviewer for his time and attention towards the manuscript.