Dear Matthew Kaiser PhD Scientific Editor BMC-series Journals BioMed Central. Dear Dr. Matthew Kaiser, I send you the corrections, according to the observations from the reviewers. I hope they are right. Below you will find the changes and corrections made. Changes Reviewer Harish Gugnani Abstract Methods 1. The first sentence “Six patients were admitted to the National Institute of Respiratory Diseases (INER) in Mexico City who presented severe respiratory symptoms suggestive of histoplasmosis” should be modified as “Six patients admitted to the National Institute of Respiratory Diseases (INER) in Mexico City presented severe respiratory symptoms suggestive of histoplasmosis”. It was modified as “Six patients admitted to the National Institute of Respiratory Diseases (INER) in Mexico City presented severe respiratory symptoms suggestive of histoplasmosis”. 2. Further by mentioning Mycobiotic agar, the authors are probably referring to what is mentioned under the Isolation and identification of H. capsulatum under the broad section of Methods. It should be so indicated in methods under Abstract.. The authors should be uniform in mentioning “Mycobiotic agar” or ““Sabouraud dextrose-agar (SDA) with antibiotics (chloramphenicol, 50 mg/L and cycloheximide, 500 mg/L)”We indicated that the cultured in “SDS” in methods under Abstract. We uniformed in mentioning “ Sabouraud dextroxe-agar (SDS) with antibiotics (chloramphenicol, 50mg/L and cycloheximide, 500mg/L” . Main Text Materials and Methods (page 9)(now page 7). The title of the second section “Isolation and identification of H. capsulatum” needs to modified as ““Isolation and identification of H. capsulatum and detection of anti-H. capsulatum antibodies” since it is included there in. The title was modified as “Isolation and Identification detection of anti-H. capsulatum antibodies”. of H. capsulatum and Results (page 10) The title of the second section” Isolation and identification of H. capsulatum” should be modified (as already suggested) under Abstract to Isolation and identification of H. capsulatum and detection of anti-H. capsulatum antibodies. The title was modified as “Isolation and Identification detection of anti-H. capsulatum antibodies”. of H. capsulatum and Table 1 The hyphens in the words “Dissem-inated” and “ histo-plasmosis” should be deleted. The hyphens in the words “Dissem-inated” and “histo-plasmosis” were deleted Minor essential revisions Abstract: Background (page 3) 3rd-Add the word “the before “two”. In this part we do not understand what you are meaning ,we do not find the word “two” Background (page 5) 2nd paragraph, 2nd line-last nut one word “template” should be changed to “temperate” (I think this is what the authors meant). The word “template was changed as “temperate” Declaration of competing interests: The sentence “the authors declare that they have no commercial or other associations that might pose a conflict of interest, no financial competing interests. :was changed as: “We declare that we have no competing interest ‘below”. Reviewer Mary Brandt The novelty of this report is still not described. As the authors state, histoplasmosis is a well-known disease throughout Mexico, but the novelty of this cluster has not been explained. We added under Abstract “It is important to report outbreaks of histoplasmosis to know the update of this disease, identifying new areas endemic and molecular characterization of the causative agents”. With this we hope to explain the importance of our study. Isolates can not be included in a particular clade unless they have been typed according to the methodology used in the description of the clade. The authors cannot state that their isolates belong to a particular clade unless the authors have been typed using all the loci. In this study the best that can be said is that the isolates are indistinguishable from each other and from the EH-317 strain. It can not be said that they are identical because only a small portion of the genome has been sampled. .… We wrote “ The isolates are indistinguishable from each other and from the EH-53” in conclusions under Abstract. Regarding point 12 of the original review, the authors have not provided any data to demonstrate their assertion that these RAPDs are reproducible. RAPDs are notoriously difficult to reproduce and this has been published by others. We wrote a letter to the reviewer to explain and provide data and papers on those reports In Fig 1, is panel B the same as panel D? If so these should be combined and panel B eliminated. The Figure legend does not describe the primers used in panel D. We eliminated the panel B and added the primers used in panel D. 1) Page 5 line 9: duboisii is misspelled. We corrected this. 2) Page 5: the Kasuga study placed H capsulatum var duboisii strains within the African clade. This should corrected. We corrected this. 3) The authors should describe where Veracruz is located within Mexico so the reader not familiar with Mexico can understand this. We added the map as figure 1 (page 7 line 8 and page 10 line 4, page 12 line24) to show where is Veracruz located. 4) Page 7: direct examination was probably not performed in SDA cultures; this should be reworded. We mentioned this observation (page 7, line 18). 5) Patients are described with disseminated histoplasmosis, yet there is no evidence provided for this. Please explain the evidence. Were liver and spleen biopsied? Were blood cultures positive?. We add the sentence “Disseminated histoplasmosis was considered when patients had hepatosplenomegaly and elevated liver enzymes, especially alkaline phosphatase” to explain this. (page 10 line 9). 6) Page 10: what are “serologic test titles? Do you mean serologic results? Page 10: the term “parasitic stage” should be removed. We corrected this, we added the titles and the word “results” (page 10, line 21). 7) Page 11 line 3: what is the meaning of the 800 200 as show We added the base-pair (bp) (now page 10 line 2). 8) Page 12 line 18: the word should be “compost” We changed the word as the reviewer indicated. 9) Page 13 line 1: serology and skin test are not really used to identify fungi. We correct this, we add the sentence “The etiological agent was clearly identified utilizing macro- and micromorphology, and assessment of anti-Histoplasma antibodies”, to explain this. (Now, page 13 line 2). 10)Page 13: similarity on dendogram does not confirm that a strain is permanently in particular area. It simply confirms that the strain was present when the patients acquired the disease. We correct this, we add the sentence “presence of the strain” (Page 13 line 19) 11)The authors speculated on a role for bat guano in spreading the organism, but they do not discuss whether there was any bat guano in the area where the patients acquired the disease. Did bats have access to the house where the patients slept? Are bats present in the area? We wrote “The house where the patients slept was surrounded by trees in which bats and migratory birds staying overnight”. We corrected and explained this observation. (Page 14 line 6) 12)Therapy: the authors should comment on why prednisone was given. According to the histoplasmosis practice guidelines (wheat et al 2007 Clin Infect Dis 45:807), the effectiveness of this treatment is not well documented. We mentioned that the reason was to avoid collateral effects and the sentence is (page 14 lines 22 and 23) “The therapeutic scheme administered to three patients was amphotericin B deoxycholate (0.7 mg/kg/day every 7 days) and methylprednisone (1 mg/kg/day every 7 days day), previous to amphotericin B administered, to avoid collateral effects; afterward, itraconazole 600 mg/day was administered for 3 days, and finally” We have made the correction as the reviewers indicated, I hope they are right. Thanks Ma. Eugenia Manjarrez Zavala.