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Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."
Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011
Dr. Shankar P.R.
"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."
Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011 Anuradha
Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.
Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020
Original article / research
Full Version
Prevalence of Genomic Resistance to Macrolide in Mycoplasma Isolates among Children with Community Acquired Pneumonia
Correspondence Address :
Dr. Sivasambo Kalpana,
1,2nd Cross St, 3rd Main Rd, Nolambur Phase 1, Chennai, Tamil Nadu, India.
E-mail: drskalpana@yahoo.co.in
Introduction: Mycoplasma pneumonia is traditionally susceptible to macrolides, tetracycline and fluroquinolones. Since, tetracycline and fluoroquinolone are used cautiously in children, macrolides remain the antibiotic of choice for treating Mycoplasma pneumonia. But, resistance to macrolides has been reported in mycoplasma since the 2000s especially from Asia. Currently, there is no evidence on macrolide resistance of Mycoplasma pneumoniae from India.
Aim: To identify the prevalence of genomic resistance to
macrolides in mycoplasma isolates among children hospitalised with community acquired pneumonia.
Materials and Methods: This descriptive cross-sectional study was conducted in Department of Paediatrics at Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu, India (tertiary care centre for children in South India), from September 2019 to August 2020. Children between 2 months to 12 years of age, who were hospitalised with community acquired pneumonia were included in the study. The sampling procedure used was induced sputum or mini bronchoalveolar lavage (in intubated children). The samples were processed for culture in Pleuropneumonia Like Organisms (PPLO) agar. The culture isolates showing the typical fried egg colonies were subjected to Polymerase Chain Reaction (PCR) to detect the presence of resistance conferring mutation in the P1 adhesin gene MPN141. Chi-square test was used to test statistical significance.
Results: Among the 268 children included in the study, mycoplasma pneumonia was positive in 33 (12.3%) cases. Mycoplasma pneumoniae was most common in children aged 1-5 years old (51.5%), followed by infants (36.4%) and children aged 5-12 (12.1%). There was no significant difference in distribution among males (39.4%) and females (60.6%) (p-value=0.08). None of the mycoplasma isolates in the study showed mutation for resistance conferring genes.
Conclusion: Macrolide resistance conferring genes were not identified in the study population, which may indicate that the mycoplasma strains from this part of India are still susceptible to macrolides.
Antibiotic, Bronchoalveolar lavage, Mycoplasma pneumoniae, Mutation, Susceptible
Mycoplasma pneumoniae infections are primarily treated with macrolides. Macrolide-resistant Mycoplasma pneumoniae (MRMp) was first reported in Japan in the early 2000s. The resistance rates increased to more than 90% within 10 years, and was then reported through Asia and finally in Europe and North America (1),(2),(3). Most cases of MRMp have been reported in children (4). Mycoplasma’s 170-kDa P1 protein is a adhesin protein that triggers a potent immune response. Mutations in the 23S rRNA for the 50S ribosome that alter the affinity for all macrolides cause mycoplasma to be resistant to this group of antibiotics. Most of the MRMp isolates demonstrate point mutations in domain V of 23S Ribosomal Ribonucleic Acid (rRNA) at positions 2058 or 2059 (Escherichia coli numbering) causing resistance to macrolides and lincosamides. Infection with macrolide resistant mycoplasma can cause clinical significant disease and worser patient outcomes when compared to Macrolide-Susceptible M. pneumoniae (MSMp) infections (5),(6).
Children with macrolide-resistant M. pneumoniae infection, experienced considerably higher fever and cough durations, as well as hospital stays and antibiotic administration, as reported by Cardinale F et al., (6). In the presence of macrolide resistance, tetracyclines or fluoroquinolones like levofloxacin, for 7-14 days are administered but these antibiotics are contraindicated in children less than 8 years old due to their side-effect profiles (7). Surveillance studies done in several countries have shown gradually increasing resistance to macrolides in mycoplasma over the past decade (7). Such study is lacking in our country although anecdotal reports of resistant mycoplasma pneumonia have been published (8).
The clinic epidemiological features of mycoplasma pneumonia observed in the study have been published earlier (9). Given the widespread usage of macrolides in the community, its critical to assess the status of macrolide sensitivity in community-acquired pneumonia in our population. Hence, this study was done to study the prevalence of genomic resistance to macrolides in mycoplasma isolates among children hospitalised with Community Acquired Pneumonia (CAP).
This descriptive cross-sectional study was conducted in Department of Paediatrics at Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu, India (tertiary care centre for children in South India), from September 2019 to August 2020. The ethical clearance was obtained from the Institute Ethics Committee (No.10092019). Informed consent was obtained from the parents. Pneumonia was defined as the presence of fever and cough along with tachypnoea or lower chest wall indrawing or both, plus presence of new infiltrate on chest radiography.
Sample size calculation: With a prevalence of mycoplasma among CAP of 22% and 95% confidence interval, sample size was calculated as 268 (10).
Inclusion criteria: Children between 2 months to 12 years of age who were hospitalised with CAP were included in the study.
Exclusion criteria: Children who had received prior treatment with antimycoplasma agents (azithromycin, clarithromycin, erythromycin and fluroquinolones-doxycycline) and any child with contraindications to sputum induction like nasal bleeding, bleeding tendencies and reduced level of consciousness were excluded from the study.
Sample collection: The induced sputum was preferred for sample collection because it is representative of the lower respiratory tract, yields a considerable amount of material for molecular analysis, and is relatively non invasive (11). In children who were ventilated with community acquired pneumonia, mini bronchoalveolar lavage done via the endotracheal tube was performed for sampling.
Procedure
Culture: The sputum samples were inoculated in Pleuropneumonia Like Organism (PPLO) agar medium with supplements and incubated at 37°C with 5% Carbon Dioxide (CO2). The PPLO agar plates were microscopically analysed for M.pneumoniae for 21 days, evaluating the morphological characteristics of PPLO colonies (fried egg appearance) as well as their staining reaction with Diene’s dye (Table/Fig 1). The mycoplasma isolates were then subjected to Deoxyribonucleic Acid (DNA) extraction and real time Polymerase Chain Reaction (PCR) analysis to detect the presence of mutation conferring P1 gene.
DNA extraction: QIAamp DNA Mini Kit (Qiagen, Germany) was used to extract genomic DNA from sputum samples. The extracted DNA was quantified using NanoDrop UV Visible Spectrophotometers at 260 nm and stored at -20ºC. Those specimens that showed growth were subjected to real time PCR to identify the nucleotide sequences that confer macrolide resistance to the mycoplasma.
Real time PCR: Real-time PCR targeting the P1 cytadhesin gene was done using Quantstudio 6 (Applied Biosystem) real-time PCR system under the following conditions: initial activation at 95°C for 2 minutes, followed by 45 cycles of 95°C for 10 s and 60°C for 30 seconds. PCR reaction mixture comprised the following components per reaction: 10 μL of probe master mix, 0.5 uM of forward and reverse primer, 0.1 uM of probe, 5 μL of genomic DNA and nuclease-free water. Macrolide resistance among the M. pneumoniae was detected using previously published probe and temperature conditions (12).
High resolution melt analysis was performed between 81ºC and 84ºC. Melting temperature for the macrolide resistant M. pneumoniae strain was higher than the macrolide susceptible strain. Appropriate positive and negative controls were included in the assay.
Statistical Analysis
The association between culture and demographic parameter, clinical feature, physical examination, antibiotic and laboratory findings were assessed by cross tabulation and comparison of percentages. Chisquare test was used to test statistical significance. A p-value <0.05 was considered statistically significant. Statistical Package for Social Sciences (SPSS); IBM version 21.0 was used for statistical analysis.
A 268 children {147 (54.9%) males and 121 (45.1%) females} were eventually included in the study out of 312 children admitted for CAP who were examined for eligibility. There were 33 (12.3%) cases of mycoplasma pneumonia. Mycoplasma pneumoniae was most common in children aged 1 to 5 years old (51.5%), followed by infants (36.4%) and children aged 5 to 12 (12.1%). There was no significant difference in distribution among males (39.4%) and females (60.6%) (p-value=0.08). Clinical characteristics of children with mycoplasma pneumonia is given in (Table/Fig 2). Macrolide sensitivity; M. pneumoniae isolated from the 33 cases by culture were subjected to PCR to detect presence of resistance conferring mutation. None of the mycoplasma isolates in the present study showed mutation for this resistance conferring gene.
Surveillance studies on macrolide resistance mycoplasma prevalence done in children have shown resistance rates of 46- 93% in Japan, 69-97% in China, 12.3-23% in Taiwan, 61.3% in South Korea, 30% in Israel, 9.8% in France, and 8.2% in the United States (13). Because its incidence decreased with the use of macrolides being curtailed, the rising prevalence of macrolideresistant M. pneumoniae may be ascribed to this practise (14).
Point mutations in domain V of the 23S rRNA gene is associated with a 103-fold to >105 fold elevation of the minimum inhibitory concentration of erythromycin when compared to susceptible mycoplasma strains (15). Substitution of adenine with guanine at base position 2063 was present in all 26 mutant sequences from a study from Singapore and is the only study on the prevalence of genotypic macrolide resistance in M. pneumoniae from Southeast Asia in current literature (16). The prevalence of genomic resistance in the mycoplasma isolates was not observed in the present study. This also correlated clinically as children in the M. pneumoniae positive group universally improved clinically. Less common mutations occurring at positions 2063 (A?T, A?C), 2064 (A?G, A?C), 2067 (A?G) and 2617 (not studied in the present study) have been reported (1),(17).
Although no macrolide resistance was observed in our study, given the widespread use of macrolide in lower respiratory tract infection, we may be in the initial stages in development of macrolide resistance which will likely increase in the next decades. The low prevalence in the study population may be due to the low prevalence of macrolide exposure. Similar low prevalence of macrolide resistance has been reported in some countries but there may be an underestimation of the spread of macrolide-resistant M. pneumoniae in countries that lack national surveillance systems for monitoring the same (18),(19). Hence, unwarranted use of macrolides should be avoided in children with community acquired pneumonia. Continued vigilance is also required to detect the development of resistance to macrolides.
To the best of authors’ knowledge, this is the first study from India studying the prevalence of genomic resistance of mycoplasma isolates from children with community acquired pneumonia. The study sampling method of induced sputum is more representative of the lower respiratory tract than nasopharyngeal aspirates, which could indicate a carrier state.
Point mutations conferring macrolide resistance, in less common sites of the P1 protein genome may need to be further be assessed in India. Guo DX et al., have reported missense mutation (K27N) in L4 ribosomal protein, mutation M144V in L4 ribosomal protein and S170P in L22 which can also confer macrolide resistance. Further studies are needed to detect such mutations (20). About 90% of M. pneumoniae infections in Asian countries like China and Japan are caused by resistant strains (21). On the other hand, in Western countries, the proportion of resistant bacteria has been relatively low, ranging from 1% to 10% (22). This variation in resistance pattern has been attributed to the judicious use of macrolides in the western countries.
Approximately 25% of patients with M. pneumoniae infection may be hospitalised due to extrapulmonary complications or severe pneumonia (23). Additionally, the prevalence and incidence of M. pneumoniae may vary in different seasons and across different geographical regions (24).
Limitation(s)
There were several limitations in the present study. Firstly, only the most common mutation conferring genomic resistance in the P1 protein gene was evaluated. There may be other mutations that are prevalent in the studied community which could alter the resistance pattern. Secondly, the genomic resistance was not correlated with in-vitro microbiological resistance in the study. So, the degree of invivo resistance to macrolides could not be reliably assessed. Thirdly, the seasonal data could not be obtained.
Genomic resistance of mycoplasma to macrolides is currently not demonstrable in children with community acquired pneumonia in the study population. Surveillance of M. pneumoniae infection is particularly important in the monitoring and treatment of community acquired pneumonia. So, authors recommend further research in this regard to ease the burden on the healthcare system in our country. More number of researches to be done in this area to get overall data of genomic resistance.
DOI: 10.7860/JCDR/2022/58540.17076
Date of Submission: Jun 18, 2022
Date of Peer Review: Jul 14, 2022
Date of Acceptance: Aug 27, 2022
Date of Publishing: Oct 01, 2022
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA
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