Title: Low prevalence of H. pylori Infection in HIV-Positive Patients in the Northeast of Brazil
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1 Author's response to reviews Title: Low prevalence of H. pylori Infection in HIV-Positive Patients in the Northeast of Brazil Authors: Andrea B Fialho (deabessalab@yahoo.com.br) Manuel B Braga Neto (mbn8w@virginia.edu) Eder J Guerra (bonfim_neto@hotmail.com) Andre M Fialho (nunesfialho@yahoo.com.br) Karine Cisne (jessicacarneiro@oi.com.br) Juliana L Sun (lucia.gastro.ufc@yahoo.com.br) Christianne F Takeda (bonfim.neto.ufc@yahoo.com.br) Igor M Silva (igorsms@hotmail.com) Dulciene M Queiroz (dqueiroz@medicina.ufmg.br) Lucia L Braga (lucialib@terra.com.br) Version: 2 Date: 4 December 2010 Author's response to reviews: see over
2 December 4 th, 2010 Dear Editors, Enclosed is the manuscript entitled Low prevalence of H. pylori Infection in HIV- Positive Patients in the Northeast of Brazil. for your consideration for publication in BMC Gastroenterology by Eder J. C. Guerra, MD; Manuel B. Braga Neto, MS; André M. N. Fialho, MD; Andréa B.C. Fialho, MD; Karine C. Fernandes, MD; Juliana L. M. Sun, MD; Christianne F. V. Takeda, MD; Igor M. Silva, MSc; Dulciene M. Queiroz, MD, PhD, Lucia L B. C. Braga, MD, PhD. We are returning the revision version of the Manuscript ID We are grateful to the reviewers for the comments and suggestions that contributed to improve the manuscript. We answered all the questions and all changes made in the text are underlined. Please, find bellow the answers to the reviewer s comments 1. In this study, H. pylori status was determined by the rapid urease test and histology. Why did not the authors use the 13C urea breathe test or H. pylori stool antigen? At that time, it was not possible to evaluate the patients H. pylori status by 13C urea breath test or H. pylori stool antigen test. Because we observed a low infection rate in the group of HIVpositive patients, in order to check our results, we evaluated by PCR the presence of H. pylori specific urea gene in paraffin wax gastric tissue from around 10 HIV-positive and -negative patients and the results were confirmed. We added a comment to the Discussion section.
3 2. As the authors discussed, the mechanism of chronic active gastritis in the gastric body in HIVpositive patients may be different from that in HIV-negative patients. Other microorganisms or some drugs using in the treatment of HIV, may play a role. Some more precise explanations will be requited in the discussion session As suggested, we improved the discussion on this subject 3. Figure 1 was not attached on the text file. We apologize and added the Figure1 4. Grammatical errors and misspellings could not be negligible. An overall revision was done, as suggested. Discretionary Revisions: 1. Methods. Staining used to stage gastritis should be described. The information was added to the M & M section. The specimens were fixed in 10% formalin, embedded in paraffin wax, and 5-µm sections were stained with hematoxylin and eosin for histology and with Giemsa staining to evaluate H. pylori status. 2. Results First paragraph. The sentence: There was no statistical difference between the groups in terms of age is not needed as groups are age matched. The sentence was deleted as suggested. 3. Results. Instead of p = (as SPSS reports), the authors should use p < We amended the text and the table 1 as suggested.
4 4. Discussion. A reference should be added to the second sentence of 3 rd paragraph ( life-long standing.). We added the reference to the Discussion section. 5. Discussion. Another interesting result is that there was no patient with intestinal metaplasia or atrophy. It may deserve comments. The data were carefully reevaluated and the lesions were observed in the corpus mucosa of seven HIV-positive and in 14 HIV-negative patients.. This finding was added to the text. 6. Discussion. Add a reference number to Fu-Jing 2007 (20, I suppose) in the last paragraph. We added the suggested reference. 7. Tables. Commas misplaced in the p-value column of all tables (0.15 instead of 0,15, for instance). It was corrected. 8. Discussion. Although high prevalence in the Brazilian Northeast is informed, no data is presented, but only the reference (17). The prevalence of the infection in the general adult population of low socio economical levels in Fortaleza is 82%. This information was added to the text. Minor Essential Revisions
5 1. Methods. Age-matched controls. The process of matching should be disclosed (exact age was used or an interval?, specific software used in the process?, patients and controls enrolled in the same period?, enrollment of controls). This explanation should also explain why the number of matched controls differed from that of cases. Patients and controls were enrolled in the same period. Ten year of age interval was used as the process of matching and the software SPSS (version 10.0, Chicago, IL) was used to confirm the adequacy of matching. The information was added to the text 2. Methods. It should be described how exposure to antibiotics was defined (current, last month, in life etc.). The exposure to antibiotics was defined as intake of antibiotics in the last six months. This information was added to the text 3. Results. The authors should provide the topographical diagnosis (for instance: H. pylori chronic active gastritis, or H. pylori antrum predominant chronic active gastritis) according to the updated Sydney System and, then, describe differences in topographical distribution of gastritis between the two groups. The results of the gastritis in the corpus and in the antrum were added to the results section. 4. Table 3 should be redesigned. We did it. Major Compulsory Revisions
6 1. Results. The total described in the 1st line (270) is wrong (total was = 254). In fact, it was a mistake. The text was amended. 2. Discussion. Information provided on ref 29 in the 6th paragraph is not exact, as mono therapy in that study eradicated 13/37 patients (35.1%). Although such a low rate precludes the clinical use of mono therapy for eradicating H. pylori, it is epidemiologically important. We agree with you and rewrote the sentences. The frequent usage of antibiotics for treatment or prophylaxis against opportunistic infections in patients at an advanced stage of HIV infection might explain the low prevalence of H. pylori infection in the patient group. However, the antibiotics most commonly used in AIDS patients are not always efficacious against H. pylori. Furthermore, low H. pylori eradication ratio is observed with the use of mono therapy, even clarithromycin that has good anti-h. pylori activity 3. Limitations of the present study should be discussed In this study, methodology limitation should be considered, since the H. pylori status was determined by only two tests (pre formed urease and histological evaluation) However, two specimens from the lesser curvature of the gastric antrum and two from the lesser curvature of the lower body were taken to avoid sampling error. These data were added to the M&M. Such fragment number has been proven sufficient to avoid false negative results according to a previous study. (Misra V, 2000) Misra V, Misra S, Dwivedi M, Singh UP, Bhargava V, Gupta SC. A topographic study of Helicobacter pylori density, distribution and associated gastritis. J. Gastroenterol.
7 Hepatol. 2000; 15: UNIVERSIDADE FEDERAL DO CEARÁ Best regards, Lucia L. B. C Braga, MD, PhD Associate Professor Department of Internal Medicine School of Medicine Federal University of Ceara
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