Fungi in a One Health Perspective

Round 1

Reviewer 1 Report

The authors presented in this piece of work a comprehensive and complete overview of the current fungal infection problematic in a holistic approach. The review is well writing and tackle all the pertinent question on the topic and the authors have compiled a large number of references to support their vision of "One Health" approach. 

For a easier reading and probably to help on the citation of the review and use of this nice material, I would suggest to include some table as summary of the finding or even if possible some figures to synthesize the idea. 

Author Response

Dear reviewer

Many thanks for helping us with this Manuscript. On behalf of the team, I am very grateful with your suggestions that were very helpful to improve our review article.

The authors presented in this piece of work a comprehensive and complete overview of the current fungal infection problematic in a holistic approach. The review is well writing and tackle all the pertinent question on the topic and the authors have compiled a large number of references to support their vision of "One Health" approach. 

For a easier reading and probably to help on the citation of the review and use of this nice material, I would suggest to include some table as summary of the finding or even if possible some figures to synthesize the idea”. 

The corrections were incorporated in the revised manuscript. Two tables and two figures were added. The new version of the manuscript is attached.

Reviewer 2 Report

This paper reviews the affects of fungi on plant, animal, and human health, as well as the affects of climate change on fungi. This is a very interesting topic and a very wide-ranging issue. I have some suggestions for this paper:

 

1. The 2-6 parts of the paper have a lot of content. I suggest using a secondary title to facilitate readers' reading. For example: 2. Fungal effects on Plant Health, I suggest using a secondary title to list the effects of fungi on plant health..

 

2. The viewpoint of the paper is not clear and the data support is insufficient. Suggest proposing clear viewpoints and listing relevant supporting data in a table format.

 

3. The paper covers a wide range of content and is lengthy, making it difficult to understand it in pure text. I suggest using figs to make it easier for  understanding.

Author Response

Dear reviewer

Many thanks for helping us with this Manuscript. On behalf of the team, I am very grateful with your suggestions that were very helpful to improve our review article. The corrections were incorporated in the revised manuscript. The following text has detailed point-to-point responses.

“This paper reviews the effects of fungi on plant, animal, and human health, as well as the effects of climate change on fungi. This is a very interesting topic and a very wide-ranging issue. I have some suggestions for this paper:

1. The 2-6 parts of the paper have a lot of content. I suggest using a secondary title to facilitate readers' reading. For example: 2. Fungal effects on Plant Health, I suggest using a secondary title to list the effects of fungi on plant health.

Response: We followed the format of the editor for review articles.

2. The viewpoint of the paper is not clear and the data support is insufficient. Suggest proposing clear viewpoints and listing relevant supporting data in a table format.
3. The paper covers a wide range of content and is lengthy, making it difficult to understand it in pure text. I suggest using figs to make it easier for understanding.”

Response: The manuscript was changed in accordance with the suggestions and two figures and two tables were added. The revised Ms is attached

Reviewer 3 Report

 

In their manuscript entitled, “Fungi in a One Health Perspective”, Simões and colleagues explore and summarize different factors -both positive and negative- of fungal species influencing/affecting human health. Overall, the article provides useful information; however, the manuscript as it stands is not ready for publication. A number of major comments and grammatical issues need to be addressed prior to publication. I recommend having the manuscript proofread and revised by a native English speaker.

Major comments.

L123. Aspergillus is not an emerging fungal pathogen. This genus has been recognized as a human pathogen for almost 2 centuries now.

L128, L185. Mycotoxins are not an emerging concern either. They have been investigated for several decades already.

L143. What about fluconazole?

L208-216. This information can be placed in a Table.

L296-301. Much of this information is repeated before.

L326 and L534. Cryptococcosis is not a zoonotic infection. Animals are considered sentinel hosts, but they DO NOT transmit the disease. Please revise this concept with appropriate literature.

L341-344 and L339-340. Specify the species in all genera. For instance, there are many species among the genus Cryptococcus, but the 2 more important, included in the fungal priority list, are C. neoformans and C. gattii. Writing “spp.” is very general and should not be used.

L346-351. The characteristic of being “immunocompetent” to be affected by C. gattii was considered for many years as a risk factor. However, in the last decade, alterations in people’s immunity, particularly anti-GM-CSF autoantibodies, have been detected in most patients affected by this species. Also, data from reference 14 should be updated with Rajasingham et al 2020. The genus Cryptococcus is intrinsically resistant to echinocandins (same as for Mucorales in L472). The whole phrase needs to be changed.

L353-355. Please organize the species of Candida in order of prevalence. Is it worldwide?

L361-365. The phrase is not clear. Which species is “the latter” if afterwards you write species in parenthesis? Parentheses are not necessary.

L371-375. C. auris was discussed before (L355-361). This should be together.

L409-411. Where was this reported?

There is much more information about Aspergillus and aspergillosis, including coinfection with virus and mutations related with antifungal resistance, than the information on Candida and, especially Cryptococcus. Why is that?

L445. The initial infection by Paracoccidioides usually occurs in the lungs. Paracoccidioidomycosis is not an implantation mycosis.

In L483 eumycetoma is mentioned. Afterwards, a number of presentations are described which have nothing to do with mycetoma. Please clarify the whole paragraph.

L514-523. This needs to be revised with other studies, not only one article. Many of the genera mentioned are not part of the mycobiome. Prescence of DNA in a sample does not mean that a microorganism is part of the mycobiome. Environmental fungi are not considered part of the mycobiome.

Please revise the use of italics in species names and the rule of writing genus-species through the text. The first time a species is mentioned, its name must include the whole genus (Aspergillus fumigatus). After that, just the first letter followed by a dot (A. fumigatus).

 

Through the text, there are many numbers and values about prevalence, incidence, number of cases, etc., of various mycoses. However, authors do noy always specify if these values are per year, in total, in the world, in a specific country, etc. This should be considered.  

Minor Comments

L46. “turn into” instead of “turn in”

L48. which, when extracted, may have… (use commas)

L53, L128. “Therefore” instead of “So”

L67. indirectly cause (without comma)

L68. fungal infections in humans

L87, L155, L206, L241. Did the authors mean “Currently” or “Actually”? If it is “Actually”, replace by “In fact”

L92. as well as

L98. Fusarium tricinctum

L100. Fusarium culmorum, Fusarium cerealis, and Fusarium avenaceum

L103. “in warmer” instead of “in the warmer”

L104. Fusarium verticillioides, Fusarium proliferatum, and Fusarium subglutinans

L117. Raising up – tons (not tones)

L119. as well as

L122. the broad use of antifungals in agriculture?

L123. like those from the genus Aspergillus

L141. large number

L51. F. verticillioides must be written in italics

L152. Fungi can also be used

L154. saprotrophs (comma), turn them INTO an…

L155-158. Rephrase the sentence, it is very confusing.

L167. Penicillium variabile, Penicillium dendriticum, and Penicillium duclauxii

L172. F. verticillioides

L186. “and/or” is not necessary

L198. has been seen (shown not showed)

L200. Which kind of samples? South Asian

L213. Asia, Middle East and North Africa

L222. spread through

L225. sex (no gender)

L237. A niger

L244. Due to

L260. inducing apoptosis in

L285. synergistic effects (remove “of mycotoxins”)

L310. even though there are

L321. Fungal infections are

L321. accounting for more than

L332 and L585. Tinea does not need italics nor capital letter

L334. Trichophyton is the genus (without spp. and singular)

L353. Candida auris, Candida albicans, (Candida glabrata), Candida tropicalis, Candida parapsilosis

L355. C. auris

L361, 364, 365, 375, 379. C. albicans, N. glabrata, C. tropicalis, P. kudriavzeveii

L366, 367. also - also – also

L367, 386. accounts for, accounting for

L377. azole-resistant

L397, 400. A. fumigatus

L405-406. Sentence needs revision

L408-409. Capital letters are not needed

L438. Fungi are not disseminated in the environment. They disseminate in the host. They are spread, found, widely distributed, etc., in the environment.

L449-452. The sentence is not clear. Authors talk about 2 mycoses and 3 regions, but give data only on one mycosis and one region.

L454. being their antifungal resistance of concern (remove is)

L456. “can cause” instead of “can result”

L475. Just one point needed after spp.

L475. L. prolificans

L482. Why is Scedosporium spp. mentioned again?

L494-495 repeats what is mentioned in L491-492

L495-498 is also repeated in the text.

L540-541. Worldwide or where?

L541. A. fumigatus s.s.

L544-545. including azole-resistant strains

L560. C. immitis or C. posadasii

L560, L624. H. capsulatum

L566. B. dermatitidis

L571. can also cause

L576. M. pachydermatis and remove “.”

L593-594. C. neoformans or C. gattii

L613. Batrachochytrium salamandrivorans

L616. Crustaceans are invertebrate animals

L260. because azoles have

L629. Do you mean antifungal susceptibility?

L643. Mucormycosis caused by which species?

L641. C. immitis

L646-651. All the species have been mentioned before. Remove the name of the genera and replace them by the initial letter.

L686. even more difficult

L699. biotechnology

L705. responsible for

L710. mortality by

L712. possibly

L713. potentially

L715. Therefore

L716. compromising

L720. regarding a

 

There are some errors in grammar that need to be addressed.

Author Response

Dear reviewer

Many thanks for helping us with this Manuscript. On behalf of the team, I am very grateful with your suggestions that were very helpful to improve our review article. The corrections were incorporated in the revised manuscript. The following text has detailed point-to-point responses.

 

“In their manuscript entitled, “Fungi in a One Health Perspective”, Simões and colleagues explore and summarize different factors -both positive and negative- of fungal species influencing/affecting human health. Overall, the article provides useful information; however, the manuscript as it stands is not ready for publication. A number of major comments and grammatical issues need to be addressed prior to publication. I recommend having the manuscript proofread and revised by a native English speaker.”

 

Major comments.

 

L123. Aspergillus is not an emerging fungal pathogen. This genus has been recognized as a human pathogen for almost 2 centuries now.

R: R: We agree that Aspergillus is recognized as a human pathogen for long time. We intended to emphasize that the number of aspergilosis cases is increasing every year to plants and humans. It was rephrased.

L128, L185. Mycotoxins are not an emerging concern either. They have been investigated for several decades already.

R: With the increasing environmental temperatures and climatic changes, it has been described that mycotoxin production can become an issue with even more relevance. The sentence of rephrased to better transmit this idea.

In L185, we consider correct the expression of “emergent mycotoxins” because only recently they were reported as harmful.

L143. What about fluconazole?

R: It has been added.

L208-216. This information can be placed in a Table.

R: Table 2 was added.

L296-301. Much of this information is repeated before.

R: In this section we discuss the control of mycotoxins production, while previously we discussed the control of fungi. As mycotoxins and some fungal species are intrinsically associated, some practices aiming to control fungal proliferation will also allow the control of mycotoxins’ production. Some text was deleted to avoid repetitions.

L326 and L534. Cryptococcosis is not a zoonotic infection. Animals are considered sentinel hosts, but they DO NOT transmit the disease. Please revise this concept with appropriate literature.

R: We agree that cryptococcosis is not conventionally considered as a zoonosis. However, several reports describe cryptococcosis transmission from animals directly to humans.

Lagrou K, Van Eldere J, Keuleers S, Hagen F, Merckx R, Verhaegen J, Peetermans WE, Boekhout T. Zoonotic transmission of Cryptococcus neoformans from a magpie to an immunocompetent patient. J Intern Med. 2005 Apr;257(4):385-8. doi: 10.1111/j.1365-2796.2005.01466.x. PMID: 15788009.

Nosanchuk JD, Shoham S, Fries BC, Shapiro DS, Levitz SM, Casadevall A. Evidence of zoonotic transmission of Cryptococcus neoformans from a pet cockatoo to an immunocompromised patient. Ann Intern Med. 2000 Feb 1;132(3):205-8. doi: 10.7326/0003-4819-132-3-200002010-00006. PMID: 10651601.

Mohammed, R., Nader, S.M., Hamza, D.A. et al. Horse: a potential source of Cryptococcus neoformans and Cryptococcus gattii in Egypt. BMC Vet Res 18, 17 (2022). https://doi.org/10.1186/s12917-021-03127-x.

L341-344 and L339-340. Specify the species in all genera. For instance, there are many species among the genus Cryptococcus, but the 2 more important, included in the fungal priority list, are C. neoformans and C. gattii. Writing “spp.” is very general and should not be used.

R: We agree with the reviewer and the sentence was rephrased.

L346-351. The characteristic of being “immunocompetent” to be affected by C. gattii was considered for many years as a risk factor. However, in the last decade, alterations in people’s immunity, particularly anti-GM-CSF autoantibodies, have been detected in most patients affected by this species. Also, data from reference 14 should be updated with Rajasingham et al 2020. The genus Cryptococcus is intrinsically resistant to echinocandins (same as for Mucorales in L472). The whole phrase needs to be changed.

R: The authors thank to the reviewer for the corrections. The sentence was rephrased and numbers updated.

L353-355. Please organize the species of Candida in order of prevalence. Is it worldwide?

R: The species were organized by their prevalence according to the references mentioned. Data on geographic distribution was added.

L361-365. The phrase is not clear. Which species is “the latter” if afterwards you write species in parenthesis? Parentheses are not necessary.

R: Corrected.

L371-375. C. auris was discussed before (L355-361). This should be together.

R: The text is organized in two parts: first we present the species epidemiology and associated diseases, then we discuss overall antifungal susceptibility profiles.

L409-411. Where was this reported? References added.

There is much more information about Aspergillus and aspergillosis, including coinfection with virus and mutations related with antifungal resistance, than the information on Candida and, especially Cryptococcus. Why is that?

R: Given the importance of azole acquired resistance from environmental sources (hotspots) Aspergillus and increasing number of aspergillosis cases caused by strains bearing mutations acquired by environmental azole exposure, we emphasize this issue due to the One Health perspective. However, we decided to delete sentences of this section.

L445. The initial infection by Paracoccidioides usually occurs in the lungs. Paracoccidioidomycosis is not an implantation mycosis.

R: In the manuscript is not referred that Paracoccidioides is considered as an implantation mycosis. Although the infection occurs mainly by inhalation, in rare cases the fungi can invade the organism by or penetration of the skin, as stated above:

“Paracoccidioides spp. are pathogenic dimorphic fungi endemic to Central and South America that live in the environment (soil). After inhalation or penetration of the skin by fungal spores from the environment, the pathogen can infect humans”

World Health Organization WHO fungal priority pathogens list to guide research, development and public health action; 2022; ISBN 9789240060241.

In L483 eumycetoma is mentioned. Afterwards, a number of presentations are described which have nothing to do with mycetoma. Please clarify the whole paragraph.

R: This section was clarified.

L514-523. This needs to be revised with other studies, not only one article. Many of the genera mentioned are not part of the mycobiome. Prescence of DNA in a sample does not mean that a microorganism is part of the mycobiome. Environmental fungi are not considered part of the mycobiome.

R: We agree with the reviewer. Novel references were added to this section and limitations associated with mycobiome detected in different body parts were added.

Please revise the use of italics in species names and the rule of writing genus-species through the text. The first time a species is mentioned, its name must include the whole genus (Aspergillus fumigatus). After that, just the first letter followed by a dot (A. fumigatus).

R: It was done.

Through the text, there are many numbers and values about prevalence, incidence, number of cases, etc., of various mycoses. However, authors do noy always specify if these values are per year, in total, in the world, in a specific country, etc. This should be considered.  

R: This information was added.

 

Minor Comments –

R: All minor comments were changed or answered according to the reviewer’s comments. All changes were done

L46. “turn into” instead of “turn in”

L48. which, when extracted, may have… (use commas)

L53, L128. “Therefore” instead of “So”

L67. indirectly cause (without comma)

L68. fungal infections in humans

L87, L155, L206, L241. Did the authors mean “Currently” or “Actually”? If it is “Actually”, replace by “In fact”

L92. as well as

L98. Fusarium tricinctum

L100. Fusarium culmorum, Fusarium cerealis, and Fusarium avenaceum

L103. “in warmer” instead of “in the warmer”

L104. Fusarium verticillioides, Fusarium proliferatum, and Fusarium subglutinans

L117. Raising up – tons (not tones)

L119. as well as

L122. the broad use of antifungals in agriculture?

R: Added: in agriculture, compost, feedstock, commodities and several other materials.

L123. like those from the genus Aspergillus

L141. large number

L51. F. verticillioides must be written in italics

L152. Fungi can also be used

L154. saprotrophs (comma), turn them INTO an…

L155-158. Rephrase the sentence, it is very confusing.

L167. Penicillium variabile, Penicillium dendriticum, and Penicillium duclauxii

L172. F. verticillioides

L186. “and/or” is not necessary

L198. has been seen (shown not showed)

L200. Which kind of samples? South Asian

R: Worldwide

L213. Asia, Middle East and North Africa

L222. spread through

L225. sex (no gender)

L237. A niger

L244. Due to

L260. inducing apoptosis in

L285. synergistic effects (remove “of mycotoxins”)

L310. even though there are

L321. Fungal infections are

L321. accounting for more than

L332 and L585. Tinea does not need italics nor capital letter

L334. Trichophyton is the genus (without spp. and singular)

L353. Candida auris, Candida albicans, (Candida glabrata), Candida tropicalis, Candida parapsilosis

L355. C. auris

L361, 364, 365, 375, 379. C. albicans, N. glabrata, C. tropicalis, P. kudriavzeveii

L366, 367. also - also – also

L367, 386. accounts for, accounting for

L377. azole-resistant

L397, 400. A. fumigatus

L405-406. Sentence needs revision

L408-409. Capital letters are not needed

L438. Fungi are not disseminated in the environment. They disseminate in the host. They are spread, found, widely distributed, etc., in the environment.

L449-452. The sentence is not clear. Authors talk about 2 mycoses and 3 regions, but give data only on one mycosis and one region.

L454. being their antifungal resistance of concern (remove is)

L456. “can cause” instead of “can result”

L475. Just one point needed after spp.

L475. L. prolificans

L482. Why is Scedosporium spp. mentioned again?

R: Changed.

L494-495 repeats what is mentioned in L491-492

L495-498 is also repeated in the text.

L540-541. Worldwide or where?

R: Worldwide.

L541. A. fumigatus s.s.

L544-545. including azole-resistant strains

L560. C. immitis or C. posadasii

L560, L624. H. capsulatum

L566. B. dermatitidis

L571. can also cause

L576. M. pachydermatis and remove “.”

L593-594. C. neoformans or C. gattii

L613. Batrachochytrium salamandrivorans

L616. Crustaceans are invertebrate animals

L260. because azoles have

L629. Do you mean antifungal susceptibility?

R : Yes, we do.

L643. Mucormycosis caused by which species?

L641. C. immitis

L646-651. All the species have been mentioned before. Remove the name of the genera and replace them by the initial letter.

L686. even more difficult

L699. biotechnology

L705. responsible for

L710. mortality by

L712. possibly

L713. potentially

L715. Therefore

L716. compromising

L720. regarding a

The revised Ms is attached

 

Kind regards

 

Round 2

Reviewer 2 Report

I have no more comments

Reviewer 3 Report

The manuscript entitled “Fungi in a One Health Perspective” improved significantly after the authors addressed major and minor comments. The inclusion of figures and tables helps as well to better read the manuscript. The work by Simões and colleagues on factors of fungal species influencing/affecting human health is ready for publication.

There are still some errors in grammar that could be addressed by the editor or during the final edition of the manuscript.