Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

Users Online : 77654

AbstractMaterial and MethodsResultsDiscussionConclusionAcknowledgementReferencesDOI and Others
Article in PDF How to Cite Citation Manager Readers' Comments (0) Audio Visual Article Statistics Link to PUBMED Print this Article Send to a Friend
Advertisers Access Statistics Resources

Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


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

Important Notice

Original article / research
Year : 2023 | Month : January | Volume : 17 | Issue : 1 | Page : DC07 - DC13 Full Version

Invasive Fungal Infections in Acute Haematological Malignancies: A Cross-sectional Study


Published: January 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/60309.17271
Anita Nandi Mitra, Prerna Pramanik, Rupsa Bhattacharya

1. Associate Professor, Department of Mirobiology, Medical College, Kolkata, West Bengal, India. 2. Post Doctoral Trainee, Department of Clinical Haematology, Medical College, Kolkata, West Bengal, India. 3. MBBS Intern, Department of Haematology, Medical College, Kolkata, West Bengal, India.

Correspondence Address :
Dr. Anita Nandi Mitra,
BD 173 Salt Lake, Sector 1, Kolkata, West Bengal, India.
E-mail: anitanandi20121964@gmail.com

Abstract

Introduction: Fungal infections are common complications of acute haematological malignancies i.e. acute myeloid and acute lymphoblastic leukaemia. The cells in these two groups are different morphologically and immunologically. Hence the interaction with the different types of fungi may vary.

Aim: To identify the acute leukaemia cases and fungal infection among myeloid and lymphoid groups and to find out association of types of invasive fungal infection according to cell line affected.

Materials and Methods: A cross-sectional observational hospital-based prospective study was conducted in a risk group of acute haematological malignancy over a period of six months from July 2021 to December 2021 in a tertiary care Hospital, Medical College Kolkata, West Bengal, India. Study tools were questionnaire based on European Organisation for Research and Treatment of Cancer /Mycoses Study Group (EORTC/MSG) criteria, clinical reports and standard laboratory procedures were practiced in Microbiology laboratory. The data was entered in excel spreadsheet and analysed using Statistical Package for the Social Sciences (SPSS) 28th version.

Results: A total of 24 cases of Invasive Fungal Infections (IFI) were observed out of the 78 patients included in the study. This corresponds to an IFI prevalence of 30.77%. Patients with proven IFI constituted 8 (33.33%), probable IFI accounted for 15 (62.5%) where as those with possible IFI accounted for 1 (4.2%) of total IFI cases. There were age and sex wise variation in IFI. The prevalence of IFI was found to be higher in Acute Myeloid Leukaemia (AML) (48.5%) patients as compared to Acute Lymphoblastic Leukaemia (ALL) (19.14%). Of all AML patients invasive candidiasis was the most common type followed by aspergillosis. In ALL patients invasive candidiasis also constituted 44.44% followed by dematiaceous mycosis, followed by aspergillosis.

Conclusion: AML patients suffer more from IFI than ALL ones. Invasive non albicans candidiasis affected both types but more incidence was seen in AML affected group. Aspergillus spp. affected lungs of both groups but dematiaceous fungi were isolated only from ALL affected paediatric patients and in samples other than pulmonary or blood sample.

Keywords

Acute lymphoblastic leukaemia, Acute myeloid leukaemia, Yeasts and molds

The IFI are common complications of the acute haematological malignancy i.e. AML and ALL. As a result of IFI the morbidity and mortality of primary disease increases along with expenditure of treatment and hospital stay (1). The development of immunocompromised state predisposing fungal infection cannot be avoided in different phases of these diseases. So the use of prophylactic antifungal is necessary to prevent the fungal invasion. For this purpose, knowledge of species of invading fungus is necessary to select right medicine/s. Neutrophils, plays a crucial role in the resistance to Candida infection may become dysfunctional in AML patients, making them susceptible to these opportunistic infections (2). Cell mediated immunity by lymphocytes is also an important factor for containment of the said infection. On the other hand, the reduction in alveolar macrophages (which prevents germination of conidia to tissue-invasive hyphae) leads to Aspergillosis (3). Antineoplastic drugs induce a neutropenic and lymphocytopenic state which predisposes patients to opportunistic mycoses (4),(5). Severe neutropenia is termed when the absolute neutrophil count is less than 500 cells/mm3 (6),(7). Opportunistic fungal infections tend to appear during this stage. Febrile neutropenia which includes severe neutropenia along with oral temperature >38.5°C or two consecutive readings of >38°C for two hours typically marks the onset of fungal infections (6). Studies have shown that older patients (≥65 years) with haematological malignancy have an increased risk of invasive fungal infections (7),(8). The critically ill patients, being treated with broad spectrum antimicrobials, and those on total parenteral nutrition, sepsis, renal insufficiency, prolonged stay in Intensive Care Unit (ICU), current stage of the malignancy (for patients not in remission) are more prone to contract such infections (3),(9). Prolonged ICU stay makes the patient more susceptible to such infections (9),(10),(11).

Increasing use of antifungal prophylaxis has led to a significant change in the mycological profile of infections (11). The data on IFI among paediatric population with ALL are still scarce in comparison to AML as has been reported (12). Inadequacy of diagnostic procedures in patients with unstable clinical situations or with a bleeding tendency (due to thrombocytopenia resulting from induction chemotherapy) delays treatment, and therefore might interfere with the patient’s survival. The aim of present study was to identify the acute leukaemia cases among admitted patients in hospital ward from clinical and laboratory record. To identify phenotypically the fungus causing IFI in such cases. To determine the association between a particular type of fungus and affected cell line.

Material and Methods

A cross-sectional observational hospital-based study was done for six months (July 2021 to December 2021) in haematology indoor wards and microbiology departments of Medical College, Kolkata. The permission required to conduct the study was given by the Institutional Ethics Committee. (IEC) with letter number- Ref No: MC/KOLIECNON-SPON/809/09/20. Study included the patients suffering from acute haematological malignancies and admitted in hospital.

Inclusion criteria

1. Consecutive non repetitive febrile patients of ALL and AML admitted in hospital were included in the study.
2. Willingness to participate in the study after giving informed written consent was considered in the study.

Exclusion criteria

1. Chronic cases of lymphoid and myeloid leukaemia.
2. Cases of acute promyelocytic leukaemia.
3. Cases of haematogical diseases other than malignancy.
4. Unwillingness to participate in the study.

Sample size: A total of 78 patients were studied as proposed.

Sample size n0=z2pq/e2 (p is the prevalence and q is 1-p.) The prevalence of fungal infections is taken to be 11% (rounded off) (12). The value for Z was found in statistical table which contains area under the normal curve. Here Z=1.96 for 95% confidence. The margin of error here is taken to be 5%.

Putting the values p=0.11, q= 0.89
Sample size=150 (for unlimited population).

However, sample size of 150 in case of period prevalence of 12 months, 75 comes for six months (from modified Cochran’s formula for smaller population).

Study tools
1. Questionnaire form prepared beforehand (Based on EORTC/MSG criteria of IFI) (13) [Annexure:1].
2. Laboratory diagnostic tools for clinical and mycological assessment.

Procedure: Questionnaire proforma was prepared by authors, the research workers [Annexure:1]. After getting written consent, subjects were first interrogated using questionnaire prepared beforehand for selecting the cases of AML and ALL and obtaining information about fungal infection. No cell line was used for research work in the laboratory. The target population was identified from records of involved myeloid or lymphoid cell line and questionnaire helped in categorising patients to proven, probable and possible IFI (or no IFI cases) (Table/Fig 1). Empirical antifungal was given in cases of febrile neutropenia for more than four days not responding to broad spectrum antibiotics. Prophylactic antifungals used in our setting was posaconazole and it was given only in selected patients (33 patients).

Clinical assessment

• The baseline data of each patient like the age, gender, the type of acute leukaemia, chemotherapeutic stage of the patient, complete blood count and drugs received by the patient were collected.
• A febrile episode is defined as oral temperature >38.5°C or two consecutive readings of >38°C for two hours. Fever was considered due to chemotherapy if it occurred within 12 hours of starting chemotherapy and resolved spontaneously in the next 24-hour period (6).
• The febrile episode was investigated for any possible source of fungal infection by taking the sample from the clinically suspected site of infection.
• Neutropenia is defined as an absolute neutrophil count less than 500 cells/mm3 (6),(7).
• The High Resolution Computed Tomography (HRCT) of chest was done for the radiological evidence of invasive fungal infection.

Sample types

• Blood sample: Biphasic blood culture medium by using Sabouraud Dextrose Agar (SDA) slant and trypticase soy broth was used.
• Sputum sample: It was induced by using nebulised sterile hypertonic saline solution.
• Urine sample: Few paediatric patients were examined.
• Bone marrow: One bone marrow sample was examined.
• Nasal mass: Evacuated mass from maxillary sinus was examined.

KOH mount: The samples were examined for fungal element under light microscope preparing 10% or 20% KOH mount (Table/Fig 2).

Fungal culture: Samples were inoculated in SDA/ Sabouraud Dextrose Chloramphenicol Agar in two sets to incubate one at 37°C and another at 25°C. For the yeasts isolates, speciation was done by VITEK 2 YST ID card. For the molds, Lacto Phenol Cotton Blue (LPCB) tease mount was examined for morphological study (Table/Fig 3).

Statistical Analysis

The data were entered in excel spreadsheet and analysed using SPSS 28th version. The p-values were calculated with Chi-square test wherever applicable.

Results

After careful analysis of the data, 24 cases of IFI were observed out of the 78 patients included in the study. This corresponds to an IFI prevalence of 30.77%. Patients with probable IFI accounted for 15 (62.5%) whereas, those with proven IFI constituted 8 (33.3%) and those with possible IFI 1 (4.2%) of IFI affected population. It was seen that highest number of proven IFI was seen in 4 (16.67%) of the patients belonging to age group 12-21 years and highest probable IFI in 4 (16.67%) of the patients of age group 22-31 years (Table/Fig 4).

Out of the 78 study subjects, 49 (62.82%) were males and 29 (37.18%) were females. Among the 24 IFI cases, proven IFI was seen in 8.33% females and 25% males. Probable IFI was present in 25% females and 37.5% males. No possible IFI was present in female while 4.2% males had possible IFI (Table/Fig 5).

Two different types of acute haematological malignancies were considered in the recruited group. Out of the 78 patients, 47 had ALL, 31 had AML. The prevalence of IFI was found to be higher in (15 out of 31) AML patients (48.4%) as compared to the 9 out of 47 ALL patients (19.47%) (p-value=0.006) (Table/Fig 6)a. Among AML patients 4 (16.66%) had proven IFI, 10 (41.66%) had probable IFI and 1 (4.16%) had possible IFI. In ALL patients 4 (16.66%) had proven IFI and 5 (20.83%) had probable IFI and no cases of possible IFI [Table/Fig-6b] (p-value 0.87).

Majority 49 (36.73%) of the patients who had undergone induction therapy developed IFI. Induction chemotherapy was found out to be a significant risk factor for the development of IFI (0.01). Neutropenia was a risk factor for IFI (p=0.04) and considering the duration of neutropenic state incidence of IFI was found in 11.76% patients having neutropenia for <10 days, 23.07%patients with 10-21days of neutropenia and 59.09% patients with >21 days of neutropenia (Table/Fig 7).

24 samples showed fungal growth after culture. Of 15 AML patients 10 invasive Candidiasis (66.7%) was the most common type followed by Aspergillosis 5 out of 15 (33.33%). In ALL patient’s invasive candidiasis constituted 4 out of 9 (44.44%) followed by dematiaceous mycosis 3 out of 9 (33.33%) followed by Aspergillosis 2 out of 9 (22.22%). As a whole, Candidiasis were identified in 14 (58.33%), Aspergillosis in 7 (29.17%) and dematiaceous mycosis in 3 (12.5%) patients. Candidiasis and Aspergillosis cases were identified in majority of AML cases whereas dematiaceous fungi were seen mainly in ALL cases (Table/Fig 8).

Lung was the commonest site of true fungi involvement accounting for 10 (41.67%) of the IFIs. Invasive aspergillosis and non albicans candidiasis caused pulmonary infections. The other site of involvement was bloodstream, constituting 11 (45.83%) of the IFIs. All bloodstream infections were due to non albicans Candida species. One (4.16%) Alternaria spp was isolated from bone marrow and maxillary sinus tissue sample of one patient and Curvularia spp. was isolated from urine of 2 (8.33%) ALL affected paediatric patients (Table/Fig 9). The prevalence of IFI in patients with antifungal prophylaxis was lower (9.09%) than those who did not receive any antifungal prophylaxis (46.66%). However, this difference (p-value=0.004) was statistically significant (Table/Fig 10).

Discussion

In the above study, the prevalence of IFI among patients with acute haematological malignancies was found to be 30.77%. This result was in agreement with previous studies showing an increased prevalence of IFI in patients with acute leukaemia affecting 11-30% in such population (1),(8),(14). Immunosuppression is seen in patients with acute leukaemia either due to disease itself or due to treatment and thus risk of IFIs develops. The humid and warm conditions in West Bengal substantially explains this finding as similar studies yielded identical result (12),(13),(14),(15). Wasylyshyn A et al., (15) showed a prevalence of IFI as 28% with proven IFI 13%, probable IFI 21% and possible IFI 66%. The prevalence of IFI was found to be higher (16.66%) among the age groups 12-41 years as compared to those at extremes of ages in present study. This was in similar with another study which have stated that the risk of IFI was higher in those <40 years. In the study by Lien MY et al., mentioned the median age of patients was 51 (range 19-76) (16). Other studies state that patients >65 years of age were at increased risk (7),(8),(12),(14),(17),(18). However, present study sample population did not include a significant proportion of representative from that age group. So it could not be commented. In present study, the prevalence of IFI was higher in men as compared to women although the difference was not statistically significant (p-value=0.59). In the study by Neofytos D et al., females were found to be at significant risk for developing IFIs p-value < 0.006 (19). This finding was unlike from the study by Hammond SP et al., getting 17.4% prevalence in male and 8.75% in females (14). Zhang R et al., and Lien MY et al., also found males to be at significant risk for developing IFI (12),(16).

The prevalence of fungal infections was found to be higher in AML (15 out of 24;62.5%) as compared to ALL (9 out of 24;37.5%) which was similar to the study by Bhatt VR et al., getting AML in 12% and ALL in 6.5% and Zhang R et al., getting AML in 11.8% and ALL in 7.1% patients (1),(12). AML has long been thought to have a higher risk of IFI than that in ALL. The recent addition of antifungal prophylaxis to induction chemotherapy has shown to significantly reduce the prevalence of IFI in AML (17). Present study confirms the same but the prevalence of IFI was not found to be significantly lower in ALL patients in this era of antifungal prophylaxis. Neutropenia for a prolonged period (>10 days) was found to be significantly associated with invasive fungal infections (13),(20),(21),(22),(23),(24),(25). Among 24 patients with IFI, 13 (59.09%) had a duration of neutropenia >21 days whereas 9 (23.07%) patients with IFI had a duration of neutropenia >10 to <21 days and 2 (11.76%) had neutropenia <10 days. Thus, a greater proportion of patients with IFI had a prolonged duration of neutropenia.

In present study majority of the IFIs were caused by non-albicans Candida species as compared to true fungi. A Taiwanese study by Lin GL et al., had also found invasive candidiasis (Candida species 59.1%) as predominant form of IFI.The increased prevalence of non-albicans Candida species as found in present study was similar to other studies by (1),(4),(5),(9),(10),(13),(20) respectively. Among these, Candida krusei infection was predominant in AML whereas Candida tropicalis invasion was seen more commonly in ALL in present study. C. glabrata and C. lucitanae infection had lower incidence rate in both AML and ALL. Neither in AML nor in ALL C. albicans was detected as agent of IFI. Hansen BA et al., mentioned of C. krusei and C. glabrata infection contributing 80% of candidiasis (20). Among the hyaline hyphae, Aspergillus fumigatus, A. flavus and A. terreus were in the list of pathogen causing pulmonary aspergillosis. In the AML patients number of cases of Aspergillosis was more than that in ALL. These fungi were isolated from induced sputum or bronchoalveolar lavage fluid. The studies have mentioned that fungus isolated from these two types of samples are to be considered as coloniser but authors considered these as pathogen as there were radiological signs of fungal invasion in lungs. The studies by Kauffman CA and Neofytos D et al., had also found such a mycological profile in those with acute leukaemia (11),(19). Aspergillus fumigatus caused 60% (n=3) of the IFIs. This was similar to other studies (3),(6),(9),(10),(13),(16),(25) where Aspergillosis varied from 10% (10) to 81.9% (16). The unusual finding of present study work was the isolation of Alternaria and Curvularia species from three cases of ALL. The Alternaria species was isolated from bone marrow aspirate and nasal mass evacuated from maxillary sinus of a sixteen-year-old girl. Curvularia lunata was isolated from urine of two boys of less than 8 years and suffering from ALL. The other studies have mentioned dematiaceous fungi causing rhionosinusitis in patients with acute hematological malignancy (18),(23). Alternaria spp. was isolated from maxillary sinus as well as bone marrow aspirate of a female patient. The Curvularia lunata was isolated from urine of a 6-year-old boy on two consecutive occasions and from another boy of 8 years on one occasion. There was no history of rhinosinusitis in these two cases.

The blood stream was the predominant site (45.83%) of IFI followed by lung (41.66%) among the patients with leukaemia. Bhatt VR et al., reported that lung was the commonest site accounting for around 75% of IFI (1). Similar reports have been made by Hansen BA et al., (20) and Tang JL et al., (26). From a 16 years old girl of ALL Alteraria spp was isolated from the bone marrow aspirate first and then from right maxilla which might be the primary site from where systemic dissemination occurred. Lastly present study isolated Curvularia lunata from urine samples of two boys suffering from ALL. No study mentioned of urine samples from where dematiaceous fungi could be isolated but presnt study found same fungus on two successive samples collected on different day.

In this study, it was found that, the prevalence of IFI was lower (9.09%) in those who had received antifungal prophylaxis than those who had not (46.6%). This difference was statistically significant (p=0.004) like the study by Zhang R et al., (12). Randomised controlled trials with prophylactic antifungals need more research work to establish the efficacy in preventing morbidity due to IFIs.

Limitation(s)

One limitation was that the study did not use any novel bio-markers and invasive procedures for the diagnosis which could have underestimated the prevalence of IFIs. Further prospective studies are therefore required to increase the external validity of present study results. A larger randomised control trial is needed to justify the efficacy of posaconazole which was the prophylactic antifungal used in present study setting. Present study did not perform the antifungal susceptibility of culture positive specimens as that facility was not available at our hospital setting which might have given a better picture of the drug resistant species in this era of antifungal prophylaxis.

Conclusion

It is evident from this study that AML patients suffered more from IFI than ALL ones. Invasive non albicans candidiasis complicated both types but more cases were seen in AML affected group. Aspergillus spp. affected lungs of both groups and dematiaceous fungi were isolated mainly from ALL affected paediatric patients. Preponderance of either yeast or mold to a particular cell line like myeloid or lymphoid was not established in present study except dematiaceous fungus. In cases of haematological malignancies, the antifungal agents are prescribed empirically to prevent fungal infection. The susceptibility of hyphal form to antifungal agents is different from that of yeasts. So present study result will help in selecting right group of antifungal agent.

Acknowledgement

Authors are grateful to the Principal, Head of the Department of Haematology and Microbiology to allow us to perform this work. Authors are also thankful to the laboratory technologists who provided us different test results.

References

1.
Bhatt VR, Viola GM, Ferrajoli A. Invasive fungal infections in acute leukemia. Therapeutic Advances in Hematology. 2011;2 (4):231-47. [crossref] [PubMed]
2.
Newburger PE, Dale DC. Evaluation and management of patients with isolated neutropenia. InSeminars in Hematology. 2013; (50)3:198-06. [crossref] [PubMed]
3.
Brooks GF, Carroll KC, Butel JS, Morse SA, Mietzner TA. Adelberg. Jawetz, Melnick, & Adelberg’s Medical Microbiology. 27th Edition. New York: McGraw Hill Medical. 2016:693-94.
4.
Ruhnke M, Böhme A, Buchheidt D, Cornely O, Donhuijsen K, Einsele H, et al. Diagnosis of invasive fungal infections in hematology and oncology-guidelines from the Infectious Diseases Working Party in Haematology and Oncology of the German Society for Haematology and Oncology (AGIHO). Annals of Oncology. 2011;23 (4):823-33. [crossref] [PubMed]
5.
Anaissie E, Grazziutti M, Nucci M. Invasive fungal infections in cancer patients. Clinical Mycology. 2nd ed. Philadelphia: Elsevier. 2009;1:431-71. [crossref]
6.
Dewan E, Biswas D, Kakati B, Verma SK, Kotwal A, Oberoi A, et al. Epidemiological and mycological characteristics of candidemia in patients with haematological malignancies attending a tertiary-care centre in India. Haematology/Oncology and Stem Cell Therapy. 2015;8 (3):99-05. [crossref] [PubMed]
7.
Lustberg MB. Management of neutropenia in cancer patients. Clinical Advances in Haematology & Oncology: H&O. 2012;10 (12):825.
8.
Auberger J, Lass-Flörl C, Ulmer H, Nogler-Semenitz E, Clausen J, Gunsilius E, et al. Significant alterations in the epidemiology and treatment outcome of invasive fungal infections in patients with haematological malignancies. Int J Hematol. 2008;88 (5):508-15. [crossref] [PubMed]
9.
Rüping MJ, Vehreschild JJ, Cornely OA. Patients at high risk of invasive fungal infections. Drugs. 2008;68 (14):1941-62. [crossref] [PubMed]
10.
Singh N. Trends in the epidemiology of opportunistic fungal infections: predisposing factors and the impact of antimicrobial use practices. Clin Infect Dis. 2001;33 (10):1692-96 [crossref] [PubMed]
11.
Kauffman CA. Fungal infections. Proceedings of the American Thoracic Society. 2006;3 (1):35-40. [crossref] [PubMed]
12.
Zhang R, Chen J, Huang H, Ma J, Meng F, Tang Y, et al. Primary fungal prophylaxis in acute leukemia patients with different risk factors: Retrospective analysis from the CAESAR study. Int J Hematol. 2017;106 (2):221-28. [crossref] [PubMed]
13.
De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European organization for research and treatment of cancer/invasive fungal infections cooperative group and the national institute of allergy and infectious diseases mycoses study group (EORTC/MSG) consensus group. Clin Infect Dis. 2008;46 (12):1813-21. [crossref] [PubMed]
14.
Hammond SP, Marty FM, Bryar JM, DeAngelo DJ, Baden LR. Invasive fungal disease in patients treated for newly diagnosed acute leukemia. Am J Hematol. 2010;85 (9):695-99. [crossref] [PubMed]
15.
Wasylyshyn A, Castillo C, Linder KA, Zhou S, Kauffman CA, Miceli MH, et al. Breakthrough Invasive Fungal Infections (IFI) in Acute Leukemia (AL) Patients Receiving Antifungal Prophylaxis. In Open Forum Infectious Diseases. 2018;5 (Suppl 1):S37. Oxford University Press. [crossref] [PubMed]
16.
Lien MY, Chou CH, Lin CC, Bai LY, Chiu CF, Yeh SP, et al. Epidemiology and risk factors for invasive fungal infections during induction chemotherapy for newly diagnosed acute myeloid leukemia: A retrospective cohort study. PloS one. 2018;13 (6): e0197851. [crossref] [PubMed]
17.
Oh SM, Byun JM, Chang E, Kang CK, Shin DY, Koh Y, et al. Incidence of invasive fungal infection in acute lymphoblastic and acute myelogenous leukemia in the era of antimold prophylaxis. Scientific Reports. 2021;11 (1):1-6. [crossref] [PubMed]
18.
Philip C, George B, Ganapule A, Korula A, Jain P, Alex AA, et al. Acute myeloid leukaemia: Challenges and real world data from India. Br J Hematol. 2015;170 (1):110-7. [crossref] [PubMed]
19.
Neofytos D, Lu K, Hatfield-Seung A, Blackford A, Marr KA, Treadway S, et al. Epidemiology, outcomes, and risk factors of invasive fungal infections in adult patients with acute myelogenous leukemia after induction chemotherapy. Diag Microbiol Infect Dis. 2013;75 (2):144-49. [crossref] [PubMed]
20.
Hansen BA, Wendelbo Ø, Bruserud Ø, Hemsing AL, Mosevoll KA, Reikvam H, et al. Febrile neutropenia in acute leukemia. Epidemiology, etiology, pathophysiology and treatment. Mediterr J Hematol Infect Dis. 2020;12 (1). [crossref] [PubMed]
21.
Lin GL, Chang HH, Lu CY, Chen CM, Lu MY, Lee PI, et al. Clinical characteristics and outcome of invasive fungal infections in paediatric acute myeloid leukemia patients in a medical centre in Taiwan. J Microbiol Immun Infect. 2018;51 (2):251-59. [crossref] [PubMed]
22.
Logan C, Koura D, Taplitz R. Updates in infection risk and management in acute leukemia. Haematology 2014, the American Society of Haematology Education Program Book. 2020;2020 (1):135-39. [crossref] [PubMed]
23.
Tuktur WR, Katzman JH, Greene JN. Curvularia sinusitis in leukemic patients: Two case reports and review of the literature. Infect Dis Clin Prac. 2022;30 (2):1-5. [crossref]
24.
Johnston DL, Lewis V, Yanofsky R, Gillmeister B, Ethier MC, Mitchell D, et al. Invasive fungal infections in paediatric acute myeloid leukaemia. Mycoses. 2013;56 (4):482-87. [crossref] [PubMed]
25.
Sezgin Evim M, Tüfekçi Ö, Baytan B, Ören H, Çelebi S, Ener B, et al. Invasive fungal infections in children with leukemia: Clinical features and prognosis.Turk J Hematol. 2022;39:94-102. [crossref]
26.
Tang JL, Kung HC, Lei WC, Yao M, Wu UI, Hsu SC, et al. High incidences of invasive fungal infections in acute myeloid leukemia patients receiving induction chemotherapy without systemic antifungal prophylaxis: a prospective observational study in Taiwan. PLoS One. 2015;10 (6):e0128410 [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2023/60309.17271

Date of Submission: Sep 18, 2022
Date of Peer Review: Oct 20, 2022
Date of Acceptance: Nov 26, 2022
Date of Publishing: Jan 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

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Sep 22, 2022
• Manual Googling: Nov 16, 2022
• iThenticate Software: Nov 21, 2022 (10%)

ETYMOLOGY: Author Origin

JCDR is now Monthly and more widely Indexed .
  • Emerging Sources Citation Index (Web of Science, thomsonreuters)
  • Index Copernicus ICV 2017: 134.54
  • Academic Search Complete Database
  • Directory of Open Access Journals (DOAJ)
  • Embase
  • EBSCOhost
  • Google Scholar
  • HINARI Access to Research in Health Programme
  • Indian Science Abstracts (ISA)
  • Journal seek Database
  • Google
  • Popline (reproductive health literature)
  • www.omnimedicalsearch.com