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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 journalsNo manuscriptsNo 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
A Study on Subsite-specific Prevalence of Candidiasis in Head and Neck Cancer Patients and its Antifungal Susceptibility Pattern: A Cross-sectional Study
Correspondence Address :
Dr. Jomon Raphael Chalissery,
Professor and Head, Department of Radiation Oncology, Amala Institute of Medical Sciences, Amala Nagar, Thrissur-680555, Kerala, India.
E-mail: joeraphael@gmail.com
Introduction: The incidence of candidiasis can vary across various subsites within the head and neck region and is associated with various co-morbidities and risk factors. The increase in the incidence of resistant Non-albicans Candida (NAC) species among these patients and the limited number of available antifungal agents make treatment difficult. A better understanding of the subsite-specific prevalence of candidiasis and its antifungal susceptibility is crucial in enhancing effective control and treatment.
Aim: To determine the subsite-specific prevalence of candidiasis among Head and Neck Cancer (HNC) patients undergoing radiotherapy.
Materials and Methods: A cross-sectional study was conducted on patients undergoing therapy for head and neck malignancies at the Department of Radiation Oncology, Amala Institute of Medical Sciences, Thrissur, Kerala, India over a four-year period (January 2019 to December 2022). A total of 276 patients aged 18 to 85 years with squamous cell carcinoma were included. Oral samples were collected from patients who developed candidiasis, and co-morbidities and risk factors were documented. Candida species were isolated and identified. Antifungal susceptibility was determined using the VITEK system, and fluconazole susceptibility was compared with the standard disc diffusion method. Data were entered into an Excel sheet and analysed using Statistical Package for the Social Sciences (SPSS) software.
Results: Pharynx was the most frequent site of head and neck malignancy, accounting for 104 cases (37.7%), followed by the oral cavity with 83 cases (30.1%). Among patients with malignancies in the pharyngeal region, a high rate of Candida infection was observed in 42 (43.3%) out of 97 cases. Candida species isolated included C. albicans (56, 57.7%), C. tropicalis (26, 26.8%), C. krusei (8, 8.3%), C. glabrata (3, 3.1%), and C. parapsilosis (4, 4.1%). Sixty-five patients (23.5%) had diabetes, which was statistically significant (p-value <0.05). All C. albicans strains were sensitive to fluconazole. The Minimum Inhibitory Concentration (MIC) of voriconazole was very low for all tested Candida species.
Conclusion: Patients with pharyngeal and oral cavity carcinomas are at an increased risk of developing candidiasis during radiotherapy. Diabetes is significantly associated with candidiasis. While C. albicans was the most common species isolated, a significant number of NAC species were also identified. Voriconazole exhibited low MIC values for C. krusei and C. glabrata, suggesting its potential as an alternative treatment option. Obtaining VITEK system identification and susceptibility reports is advisable for borderline values that may not be evident using conventional disc diffusion methods.
Candida albicans, Candida glabrata, Fluconazole, Pharynx, Radiotherapy, Voriconazole
Candidiasis, a fungal infection caused by the Candida species, is a common complication in individuals with HNC (1),(2),(3). The prevalence of candidiasis can vary among different subsites within the head and neck region, including the oral cavity, pharynx, larynx, nasal area, and the salivary glands (4). Complications associated with candidiasis, such as pain, swallowing difficulties, and compromised nutrition, can significantly impact the well-being of HNC patients (5). Oral candidiasis is frequently observed in individuals with diabetes, as Candida thrives in an environment promoted by heightened blood sugar levels. Despite diabetes being closely associated with systemic problems like hypertension and kidney disease in immunocompromised patients, the direct association with causing candidiasis is evident primarily among individuals with diabetes (6),(7),(8). Tobacco use is associated with a high rate of Oropharyngeal Candidiasis (OPC), and alcohol consumption has been linked to the development of cancer of the oral cavity and pharynx (9),(10),(11). By understanding the cancer subsites with a higher prevalence of candidiasis, healthcare professionals can focus on improving oral health, swallowing function, and overall quality of life in the most affected areas (12),(13).
Over the past few years, there has been a significant rise in the occurrence of infections among immunocompromised patients caused by NAC species. This increase is either equivalent to or surpassing the prevalence of the widely recognised pathogen, C. albicans (4),(14). Azole antifungal drugs are most commonly used in the treatment of oral Candida infections due to their efficacy, oral bioavailability, and tolerability. However, NAC species are more resistant to fluconazole, the most commonly used azole group of antifungal drugs, which makes treatment challenging (15),(16). As the availability of antifungal medications is limited, addressing resistant Candida infections is progressively becoming more challenging. There is a scarcity of information regarding the distribution of candidiasis in specific subsites within the head and neck region and the effectiveness of the various available antifungal agents against C. albicans and NAC strains among HNC patients in this region, where there is a rise in the burden of HNC (17),(18).
A better understanding of the subsite-specific prevalence of candidiasis and its antifungal susceptibility is crucial in enhancing effective control and treatment. The aim of the present study was to identify the subsite-specific prevalence of candidiasis among HNC patients undergoing treatment. The primary objective of the study was to find its association with co-morbidities and risk factors and to detect the antifungal susceptibility of the isolates. The secondary objective of the study was to determine the distribution of Candida species among HNC patients, determine the Minimum Inhibitory Concentration (MIC) of six antifungal agents against the Candida isolates, and compare fluconazole susceptibility using the standard disc diffusion method to provide insights into the reliability of the standard approach in determining fluconazole susceptibility in HNC patients.
A cross-sectional study was conducted at the Department of Radiation Oncology, Amala Institute of Medical Sciences, Thrissur, Kerala, India, on patients undergoing Radiation Therapy (RT) for head and neck malignancies. The study was conducted over a four-year period from January 2019 to December 2022.
The study protocol was presented to the Institutional Ethics Committee (IEC), and approval was obtained (Ref No. 30/IEC/19/AIMS-11). All participants were provided with information about the study and gave their written consent.
Inclusion criteria: Patients with proven squamous cell carcinoma of the head and neck region were included in the study.
Exclusion criteria: Patients who were on antifungal therapy and below 18 years of age were excluded from the study.
Sample size: The study aimed to investigate candidiasis among 276 patients with head and neck malignancies, showing a prevalence ranging from 25-35% (3),(19). Therefore, using an average prevalence (P) of 30%, precision (d) as 20% of prevalence, and a significance level (α) of 5%, the minimum sample size was calculated as 224.
n=(Z1-α12)2 pq/d2
Study Procedure
Swabs were collected from the oropharyngeal region and sent to the microbiology laboratory for preliminary isolation and identification. KOH mounts were prepared to check the presence of yeasts and pseudohyphae. Samples were cultured on Sabouraud’s dextrose agar and Hichrome agar (HiMedia Laboratories Pvt., Limited., Mumbai, India) plates and incubated at 37°C for 24-48 hours. Gram staining was performed for the preliminary identification of Candida (20). Fresh subcultures were then performed on SDA plates to obtain pure cultures for VITEK® 2 Systems identification and MIC detection. Additionally, fluconazole susceptibility was determined using the conventional disc diffusion method. Underlying conditions such as diabetes and hypertension were observed, and factors contributing to the risk, such as tobacco and alcohol use, were documented.
Identification and susceptibility testing using the VITEK® 2 Compact System were conducted following the manufacturer’s instructions. Inoculum was prepared in sterile saline provided by the manufacturer, with a turbidity range between 1.80-2.20 McFarland standard, as per bioMérieux VITEK® 2 DensiCHEK? instrument. VITEK® 2 YST cards were used for identification testing, while VITEK® 2 AST-YS08 cards were used to determine the susceptibility of the yeasts to antifungal agents. The VITEK® 2 AST-YS08 card contained different concentrations of various antifungal agents, including amphotericin B, caspofungin, flucytosine, micafungin, voriconazole, and fluconazole. MIC values were interpreted according to the breakpoints stated in CLSI M27-M44S (21).
Fluconazole susceptibility was tested and interpreted using the standard disc diffusion method, following CLSI M44-A2 guidelines (22). Fluconazole discs (25 μg) were obtained from HiMedia Labs, India. Mueller-Hinton agar supplemented with 2% glucose was 10used for sensitivity testing. Microbial Type Culture Collection (MTCC) 3017 from the Institute of Microbial Technology, Chandigarh, India, was used as the control strain.
Statistical Analysis
The data were analysed using SPSS software (v23, IBM, Illinois, US). Continuous measurements were reported as the mean±Standard Deviation (SD). Categorical measurements were presented as numerical counts along with their respective percentages. The association between co-morbidities and risk factors with candidiasis was determined using the Chi-square test.
The study included 276 patients with HNC. The age range was 31 to 85 years, with an average age of 65. The majority of the patients were men, accounting for 231 (83.7%) cases, with an average age of 65. Women comprised 45 (16.3%) of the patients, with an average age of 65 years. In the current study, the pharynx was the most frequent site of head and neck malignancy, with 104 (37.7%) cases. This was followed by the oral cavity with 83 (30.1%) cases, the larynx with 74 (26.8%) cases, the nasal cavity and paranasal sinuses with 8 (2.9%) cases, and the salivary glands with 7 (2.5%) cases of parotid malignancies observed (Table/Fig 1).
Candidiasis was identified in 97 (35.1%) out of 276 patients, with the most prevalent species being C. albicans in 56 (57.7%) cases. Other NAC species, are shown in (Table/Fig 2).
Various Candida colonies of C. albicans, C. tropicalis, C. krusei, C. glabrata, and C. parapsilosis were seen on the Hichrome agar plate, as shown in (Table/Fig 3).
In the study, 65 (23.5%) patients were diabetic, and among them, 41 (63.1%) had candidiasis. The association between diabetes and oral candidiasis (OPC) was found to be statistically significant (p=0.0001). However, there was no significant association with risk factors like tobacco and alcohol (p-value >0.05) (Table/Fig 4).
Among the patients with malignancies in the pharyngeal region, a high rate of Candida infection was observed, specifically in 42 (43.3%) out of 97 patients, including 5 (11.9%) out of 42 in the nasopharynx, 22 (52.4%) out of 42 in the oropharynx, and 15 (35.7%) out of 42 in the hypopharynx. Additionally, 37 (38.1%) out of 97 patients with oral cavity malignancies were found to have Candida infection. A total of 16 (16.5%) out of 97 patients with cancer in the laryngeal region had candidiasis (Table/Fig 5).
Candida albicans strains isolated were sensitive to fluconazole by the standard disc diffusion test and to all six antifungal agents tested using the VITEK® 2 Compact System. C. tropicalis and C. parapsilosis strains showed 100% susceptibility to fluconazole by the disc diffusion method, as well as to all six antifungals by the VITEK® 2 Compact System. C. krusei strains are inherently resistant to fluconazole, and C. glabrata strains show acquired resistance. The MIC to voriconazole was very low for all the Candida species tested. All the strains were sensitive to micafungin and amphotericin B. Out of the eight C. krusei strains, 2 (25%) showed intermediate susceptibility, and 2 (25%) were resistant to Caspofungin, and all of them were resistant to Flucytosine by the VITEK® 2 Compact System (Table/Fig 6).
The occurrence of oral candidiasis is prevalent in individuals with diabetes, and it has been observed that higher blood sugar levels create a favourable environment for Candida growth. The interplay between hyperglycaemia, impaired immune response, dry mouth, and altered microbial balance contributes to the increased susceptibility to oral candidiasis in individuals with diabetes (23),(24). In the present study, a significant association between diabetes and HNC was found. Out of a total of 65 (23.5%) diabetic patients, 41 (63.1%) had candidiasis during the course of treatment. Gong Y et al., and Abhinav RP et al., in their studies have found evidence indicating an increased risk of developing oral cancer in patients with diabetes and also a higher mortality rate among them (25),(26). Proper management of blood sugar levels, along with appropriate antifungal therapy, is crucial in preventing and treating oral candidiasis in diabetic patients.
According to a study conducted by Bagnardi V et al., it has been demonstrated that even small amounts of alcohol consumption are linked to the development of oral cavity and pharynx cancer, as well as oesophageal cancer (11). In the present study, the highest incidence of cancer was observed in the pharyngeal region, with 104 (37.7%) cases, followed by cancer in the oral cavity with 83 (30.1%) cases. This finding was comparable to a recent study by De Vasconcellos Ferreira PM et al., where the oral cavity accounted for 28 (42.4%) cases and the pharynx accounted for 23 (34.8%) cases (27). However, in the current study, no significant association was found between known risk factors such as tobacco and alcohol consumption. Various studies have indicated a notable increase in the incidence of oropharyngeal cancer in several countries, suggesting that the positive trends in oral and pharyngeal cancer mortality and incidence in certain countries worldwide can be attributed to changes in tobacco and alcohol consumption among men over the past few decades (9),(10),(28).
In this particular study, C. albicans was identified as the most commonly isolated Candida species, followed by NAC species such as C. tropicalis, C. krusei, C. glabrata, and C. parapsilosis. Similar findings were reported in studies conducted by Wu J et al., where 53.2% of the isolates were C. albicans followed by NAC species like C. tropicalis, C. krusei, and C. parapsilosis, and E Silva VC et al., where C. albicans was the most prevalent species isolated (29),(30). A study conducted in the southern part of India also reported findings consistent with the pattern of isolation observed in this study, with C. albicans being the most prevalent fungal species isolated. NAC species isolated in their study were C. tropicalis, C. krusei, C. glabrata, and C. parapsilosis (31). However, a separate study conducted in the eastern part of India revealed that NAC species were more prevalent, with C. parapsilosis being the most frequently identified species in that particular region (32).
In the present study, all the C. albicans strains isolated were susceptible to fluconazole by both disc diffusion and the automated method. Generally, C. albicans exhibits good susceptibility to commonly used antifungal agents such as fluconazole, itraconazole, and voriconazole. However, there have been reports of increased resistance to azole antifungals, especially in certain geographic regions or among patients with prior antifungal exposure. NAC species, such as C. glabrata, C. tropicalis, C. krusei, and C. parapsilosis, have shown varying patterns of antifungal susceptibility. C. glabrata is known to have higher acquired resistance to azole antifungals, while C. krusei is often intrinsically resistant to fluconazole. The VITEK® 2 compact system indicated that both of these strains in the present study were resistant to fluconazole. Voriconazole, a triazole antifungal drug, exhibits enhanced antifungal activity compared to fluconazole and is effective against all Candida species, including C. krusei and C. glabrata, which are inherently resistant to fluconazole, as well as fluconazole-resistant C. albicans strains (33),(34). In this study, all the strains of C. krusei and C. glabrata exhibited significantly low (MIC values for voriconazole). Therefore, voriconazole can be considered as a viable alternative drug option for the treatment of infections caused by these specific Candida species. Normally, C. tropicalis and C. parapsilosis show good susceptibility to azole antifungal drugs, although there have been reported cases of resistance. In the current study, the C. tropicalis strains were found to be pan sensitive, but their susceptibility to fluconazole was at the borderline level as indicated by the MIC values. All C. parapsilosis strains were sensitive to all the tested drugs, which was in concordance with the results of the study by Erum R et al., (35).
Limitation(s)
The study included patients exclusively from a single centre. Nevertheless, considering the limited availability of related studies in the current literature, these findings may still hold relevance in the management of OPC in HNC patients undergoing RT.
Patients receiving RT for pharyngeal and oral cavity carcinoma are at an increased risk of developing candidiasis during the course of their treatment. There is a notable association between diabetes and the risk of Candida infection in HNC patients. However, this study did not find an association between alcohol and tobacco use and the occurrence of oral cancer, which could possibly be attributed to changes in lifestyle. Although C. albicans was the most commonly found Candida species, a considerable number of NAC species were also identified. All the C. albicans strains showed sensitivity to fluconazole. Voriconazole exhibited very low MIC values for C. krusei and C. glabrata, suggesting it can be considered as an alternative option for treating infections caused by these strains.
It is advisable to obtain VITEK system identification and susceptibility reports whenever possible, as they can provide insight into borderline values that may not be evident when using conventional disc diffusion methods.
The authors are grateful to Dr. Ajith TA, Professor, Department of Biochemistry, Amala Institute of Medical Sciences, for his valuable help during the preparation of this manuscript.
DOI: 10.7860/JCDR/2023/66418.18509
Date of Submission: Jul 07, 2023
Date of Peer Review: Aug 11, 2023
Date of Acceptance: Sep 05, 2023
Date of Publishing: Oct 01, 2023
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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