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

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Dr Mohan Z Mani

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On Sep 2018




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Prof. Somashekhar Nimbalkar
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Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
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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."



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Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
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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.
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Professor and Head
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Saraswati Dental College
Lucknow
On Sep 2018




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




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Best regards,
C.S. Ramesh Babu,
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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 : 2012 | Month : May | Volume : 6 | Issue : 3 | Page : 388 - 392 Full Version

Prevalence of Cryptococcal Meningitis among Immuno-competent and Immuno-compromised Individuals in Bellary, South India: A Prospective Study


Published: May 1, 2012 | DOI: https://doi.org/10.7860/JCDR/2012/.1989
Kanchan Mahale, Satish Patil, Ravikumar, Nagabhushan, Ramanath Mahale

1. Corresponding Authors, 2. Assistant Professor, Dept of Microbiology, S.D.M.Medical college, Dharwad, India 3. Professor and Head, Dept of Neuromicrobiology, NIMHANS,Bangalore, India. 4. Professor,Dept of Medicine, VIMS,Bellary, India. 5. Assistant Professor, Dept of Paediatrics, Srinivas Institute of Medical Sciences and research centre, Surathkal Vijayanagar Institute of Medical Sciences, Bellary, India.

Correspondence Address :
Kanchan Mahale,
Assistant professor,Department of Microbiology,Srinivas
Institute of Medical Sciences and Research Centre, Surathkal,
Mangalore, India.
Phone: 9480137769/9449916162
E-mail: dr.kanchu@gmail.com

Abstract

Background and Objectives: Cryptococcal meningitis is now the leading cause of community acquired meningitis. It has generally been thought to be associated with individuals with AIDS. However, other predisposing factors like leukaemia, lymphoma, Diabetes mellitus, connective tissue disorders and organ transplantation also contribute to this infection. Cryptococcal meningitis also occurs in apparently immuno-competent individuals. Opportunistic infections are the major life threatening complications of the acquired immuno-deficiency syndrome (AIDS). An early diagnosis can help the clinician to treat cryptococcal meningitis and to thus help in reducing the rate of mortality. The present study was taken up to evaluate the occurrence of cryptococcal meningitis among immuno-compromised and immuno-competent individuals and also to analyze the predisposing factors which contribute to its occurrence.

Methods: A total of 242 CSF samples of clinically suspected cryptococcal meningitis were screened for Cryptococcus neoformans irrespective of their immune status. Their identification was based on direct microscopy, culture and biochemical reactions which were carried out by conventional methods. The CD4 cell count was obtained by flow cytometry in all the culture positive patients.

Results: The overall prevalence of cryptococcal meningitis was 8.3% and the prevalence of cryptococcal meningitis among the immuno-compromised patients was found to be 16.6%. 60% of the patients were in the age group of 21-40 years. Infection with HIV (100%) was the most common predisposing factor, followed by diabetes mellitus (40%), chronic smoking (20%) and prolonged steroid therapy (5%). Cryptococcus neoformans var. neoformans was the aetiologic agent in all the culture positives in our study. Cryptococcal meningitis was the AIDS defining illness in 50% of the patients. The mean CD4 count was 59.55. 65% of the patients had a CD4 count of <100.

Conclusion: The high prevalence of cryptococcal CNS infections in HIV infected patients underscores the importance of a precise and early microbiological diagnosis. A high index of clinical suspicion and mycological surveillance is required to help in an early diagnosis and appropriate therapy.

Keywords

Cryptococcal meningitis, AIDS, Immunocompromised,Cryptococcus neoformans, CNS infections

Introduction
Cryptococcosis was considered as a clinical rarity in the early 1900s (1). The number of cases of cryptococcosis has dramatically increased since the 1950s. This increase has resulted partly from the greater awareness about Cryptococcus neoformans as a human pathogen, but mostly it parallels the ever-enlarging population of immuno-compromised individuals as a result of aggressive chemotherapies, organ transplantations and the acquired immunodeficiency syndrome (2). Cryptococcus neoformans is the second most common lethal fungal opportunist after Candida albicans, which causes symptomatic cryptococcosis in 6–13% of the patients with AIDS (1),(4),(2),(6). C. neoformans, the causative organism, is ubiquitous in distribution. A vast majority of the isolates which are responsible for infections are of the C. neoformans var. neoformans serotype A (3). The organism gains access into the host usually via the respiratory route and it is generally contained there by an intact cell mediated immune system. However, in the presence of immunodeficiency, C. neoformans disseminates widely especially to the central nervous system (CNS) (4). It has a special propensity for invading the CNS. Meningitis is the commonest CNS manifestation of a cryptococcal infection (4). It presents as a sub-acute or chronic illness without overt meningeal disease or encephalopathy (5). The diagnosis is established by CSF analysis which demonstrates the organism on India ink preparation or culture. Cryptococcal meningitis is an important fatal infection of the CNS, wherein, the signs and symptoms are indistinguishable from those of other sub acute and chronic CNS infections. An early diagnosis can help the clinician to treat cryptococcal meningitis and it thus helps in reducing the mortality rate. It is generally thought to be associated with individuals with AIDS. However, other predisposing factors like leukaemia, lymphoma, diabetes mellitus, non-insulin dependent diabetes mellitus (NIDDM), connective tissue disorders and organ transplantation also contribute to the infection (4). Cryptococcal meningitis also occurs in apparently immunocompetent individuals (4).

The perceived importance of C. neoformans as a human pathogen, has led to the species being subjected to intense study during the last decade. The present study was taken up to study the occurrence of cryptococcal meningitis in immunocompromisedand immunocompetent individuals in the Bellary region of south India. The patient’s demographic data, the predisposing factors for cryptococcal meningitis, the risk factors for acquisition of the HIV infection, AIDS defining conditions, other concurrent infections, the presenting clinical symptomatology, physical findings, laboratory parameters and the cerebrospinal fluid (CSF) examination findings were analyzed in relation to its occurrence.

Material and Methods

This study was carried out in the Department of Microbiology, Vijayanagar Institute of Medical Sciences, Bellary, India from December 2007 – December 2008. The catchment area of the patients who attended this hospital was predominantly the Bellary district and the neighbouring districts. A total of 242 CSF samples were processed during the study period. Clinically suspected cryptococcal meningitis cases, irrespective of their immune statuses were included in the study. Meningitis cases which were caused by other aetiologies were excluded from the study. All the CSF samples were collected before instituting the therapy. The samples were considered as a potential biohazard and they were handled with care by using universal precautions. A haemogram and a CD4 cell count was perfomed in all the patients who were involved in the study. The samples were subjected to the evaluation of their cell count and cell types, proteins and sugar, direct microscopy by the India ink preparation, gram staining and culture for speciation and biotyping.

The CSF samples were inoculated on duplicate sets of Sabouraud’s dextrose agar (SDA) slopes which were devoid of cycloheximide for the culture. They were incubated at 25oC and 37oC, separately over a period of four weeks. The cultures which yielded smooth, cream-buff coloured, moist and mucoid colonies at 37oC were considered as positive. The suspected colonies on SDA were confirmed by doing gram staining and India ink preparations. The following biochemical tests were performed for the speciation of the isolates. A. The Urease test: The Urease test was performed by using Christensen’s urea agar with a phenol red indicator (6). B. The Inositol assimilation test: It was performed by using a yeast nitrogen base with a bromocresol purple indicator (7). C. The Test for phenol-oxidase: It was performed by using Staib’s bird seed agar (8).

Biotyping of the isolates was done by using Canavanine Glycine Bromothymol blue (CGB) agar. The CGB agar was prepared according to Kwon Chung et al’s method (9). The CD4 cell count was obtained by flow cytometry, by using a BD FACScount machine. Cryptococcal meningitis was diagnosed by checking for the clinical features of meningitis/meningoencephalitis and by checking for a positive CSF India ink preparation and/or the isolation of C. neoformans in the CSF culture. Patients who presented with the clinical features of meningitis/meningoencephalitis of less than four weeks duration were defined as having an acute or a subacute presentation. The following criteria were used to define the common concomitant infections: Pulmonary tuberculosis (PTB): The clinical features which were suggestive of TB with radiological features were compatible with TB on chest radiographs or computed tomographic (CT) scans, the demonstration of acid-fast bacilli (AFB) in the sputum smears or the growth of Mycobacterium tuberculosis in the sputum cultures. Pneumocystis jiroveci pneumonia (PCP): Bilateral, diffuse interstitial infiltrates on chest radiographs or high-resolution CT, with hypoxaemia (PaO2 <12 kPa), sputum smears/cultures which were negative for aerobic bacteria and AFB and/or the demonstration of Pneumocystis jiroveci in the induced sputum.

A descriptive statistical analysis was carried out in the present study. The results of the continuous measurements were presented as mean = SD (min-max) and the results of the categorical measurements were presented as percent. The significance was assessed at a 5% level of significance. The prevalence of Cryptococcal meningitis (culture positivity) was estimated and its prevalence was correlated according to the age, gender, marital status, partner status, CSF analysis and the CD4 count analysis of the patients by using the single proportion test. The diagnostic statistics viz: sensitivity, specificity, positive predictive value, negative predictive value and accuracy were computed for evaluating the India ink method results against the culture positivity. The statistical softwares, namely, SPSS 15.0, Stata 8.0, MedCalc 9.0.1 and Systat 11.0 were used for the analysis of the data and Microsoft word and Excel were used to generate the graphs and the tables.

Results

The study population consisted of 242 patients, of which 168 were males and 74 were females. Of the 242 patients, 122 patients were immunocompromised and 120 of them were immunocompetent. The demographic profile of the study population is shown in (Table/Fig 1). Among the 242 patients, C. neoformans var. neoformans was isolated in 20 patients. Twenty patients who were diagnosed to have cryptococcal meningitis were analyzed. All of them had a compromised immune status. Cryptococcal meningitis was not prevalent in the immunocompetent patients. The immunocompromised state was significantly associated with the culture positivity (Table/Fig 2). The overall prevalence of cryptococcal meningitis in the study population was 8.3% and that in the immunocompromised group was 16.6%. The mean age of presentation was 28.6+6 years. Most of the patients (95%) were in the age group of 21-40 years (Table/Fig 1). None of the patients were above the age of 40 years. Among the culture positives, 55% of the patients were males. The male: female ratio was 1.2:1.

Infection with HIV (100%) was the most common predisposing factor, followed by chronic smoking (50%), diabetes mellitus (40%) and prolonged steroid therapy (5%) (Table/Fig 3). Cryptococcal meningitis was the initial presenting illness of an HIV seropositive status in 50% of the patients. Two (10%) patients had associated pulmonary tuberculosis, two (10%) had oral candidiasis, two (10%) patients had bronchopneumonia (Pneumocystis jeruveci) infection and one (5%) patient had herpes zoster infection. An identifiable risk factor for the HIV infection was present in 11 (55%) patients. Eleven (55%) patients were from the high risk groups, which included truck drivers and intravenous (IV) drug abusers. The commonest mode of transmission was multiple, heterosexual, unprotected sexual contact, which was seen in nine patients. One patient each had a history of unsafe blood transfusion and intravenous drug abuse.

Headache was the most common presenting symptom. It was present in 85% of the patients. In all the patients who had headache, it was found to be of severe intensity and it was situated bi frontally. Vomiting was the second most common presenting symptom, and it was seen in 80% of the patients. Low grade fever was present in 60 % of the patients. The other presenting symptoms included an altered sensorium (40%), seizures (20%) and motor deficits (10%). Most of the patients (75%) had symptoms of less than fourweeks duration (acute – subacute); 25% of patients presented with chronic meningitis. The CD4 cell count in our study ranged from 10 to 156 cells/μl. The median CD4 cell count of the whole group was 59.55 cells/μl. Twenty per cent of the patients had a CD4 count of less than 50 cells/dl and 65% of the patients had a CD4 count of less than100cells/dl.

Culture was taken as the gold standard against which the India ink preparation was compared. The sensitivity, specificity, positive predictive value, negative predictive value and the accuracy of the India ink preparation were 90%, 100%, 100%, 99.1% and 99.2% respectively. (Table/Fig 4), (Table/Fig 5). The India ink preparation of CSF was positive in 90 % of the patients. The cryptococcal culture of CSF was positive in all the 20 patients. All the positive cultures yielded C. neoformans var. neoformans. Since Cryptococcal meningitis was prevalent only in immunocompromised patients in our study, a comparison could not be done between the two groups.

Discussion

The prevalence of cryptococcal meningitis varies world wide, ranging between 6-13% in patients with AIDS (1),(2),(10). In the present study, cryptococcal meningitis was seen predominantly in immunocompromised individuals. It was not prevalent in immunocompetent patients. Cryptococcal meningitis is generally considered to be rare in immunocompetent patients and the diagnosis is often delayed because of the presence of non-specific symptoms. The overall prevalence of cryptococcal meningitis in the present study was 8.3%, which was similar to the findings of the studies which were done elsewhere in India and abroad (11),(12). Cryptococcal meningitis may affect persons of any age. However, the average age of the patients ranges from 30-40 years. In the present study, the patients had a mean age of 28.6+6 years, with 95% of the patients being in the age group of 21-40 years, the most productive age group in the country. This was in consonance with the technical report which provided the national level statistics, which was published by the National AIDS Control Organization (NACO) in the year 2006.

Cryptococcal meningitis is more frequently reported in men than in women and rarely in children (13). This may reflect a difference in the exposure rather than a difference in the susceptibility. In the present study, the number of males was more as compared to the number of females (1.2:1). This is in accordance with the findingsof other studies, which had demonstrated a higher prevalence of cryptococcal meningitis in men (14) In the present study, while the males belonged to a wider age spectrum, the females were of a considerably younger population, and most of them had acquired the infection from their spouses, thus reflecting the male dominance in the Indian society. This emphasizes an increased need for awareness and counseling of both the spouses. Cryptococcal meningitis is generally thought to be associated with individuals with AIDS. However, other predisposing factors like leukaemia, lymphoma, diabetes mellitus, connective tissue disorders and organ transplantation may also contribute to the infection. In the present study, cryptococcal meningitis was prevalent only in immunocompromised patients; the infection with HIV being predominant, followed by diabetes mellitus, chronic smoking and prolonged steroid treatment. In the present study, among the 20 culture positives, all the 20 patients were found to be HIV seropositive; of which 50% of the patients had been found to be HIV seropositive during prior admission for pulmonary tuberculosis, oral candidiasis and herpes simplex infection. Cryptococcal meningitis was the first manifestation of AIDS in 50% of the patients. In other words, cryptococcal meningitis was the AIDS defining illness in 50% of the patients. This finding is almost similar to that of the study which was done by Chuck et al.,(5) wherein cryptococcal meningitis was the AIDS defining illness in 45.28% of the patients. In this study, two patients had associated pulmonary tuberculosis, one patient had oral candidiasis, two patients had bronchopneumonia and one patient had herpes zoster infection. This was in consonance with the findings of two large studies on HIV-infected patients which were reported from the Indian subcontinent (15),(16).

The triad of headache, fever and vomiting were the predominant symptoms, which were similar to the earlier reports in the literature (17),(18). Headache was the most common presenting symptom. It was present in 85% of the patients. In all the patients who had headache, it was found to be of severe intensity and it was situated bi frontally. Cryptococcal meningitis usually presents in the form of chronic meningitis. In the present study, more than half the patients had an acute to a subacute presentation. This emphasizes that even with an acute presentation along with the features of meningitis in HIV-infected individuals, the possibility of cryptococcal meningitis must always be considered and that the patients must be investigated accordingly. The clinical presentation of cryptococcal meningitis in an indolent manner with fever and headache, with absence of the signs of meningeal irritation in more than 80% of the cases, necessitates a high index of suspicion. The diagnosis of cryptococcal meningitis was based on the CSF culture. Among the 20 culture positives, the India ink preparation showed positive results in 18 patients. In one out of the 18 patients, the India ink staining showed numerous capsulated budding yeast cells in CSF. In other cases, we had to diligently search all the fields of the smear from the deposit before it could be considered as positive. The CSF India ink preparation was positive in 90% of the patients. The CSF culture was superior to the India ink staining. By considering culture as the gold standard, the sensitivity of the India ink preparation was found to be 90%. The India ink preparation is a simple procedure and it is used as a screening procedure in cases of cryptococcal meningitis. The positivity in the present study with respect to the India ink preparation was similar to that of the studies which were done by Imwidthaya et al.,(19) Darras-Joly et al., (20) Kovac et al. and Thakur et al (21). The CSF culture for C. neoformans is the diagnostic gold standard test.

A vast majority of the isolates which were responsible for the cryptococcal infection were of the C. neoformans var. neoformans serotype A (3). Cryptococcus neoformans var. neoformans was found to be the aetiologic agent in all the culture positives in our study. It was possible that exposure to the neoformans variety was more common than the exposure to the gattii variety. This was therefore an epidemiologic problem which was closely associated with the geographic topography which was specific to the ecological niches of these two varieties. The Neoformans variety was found in pigeon droppings. The CD4+ T cell count was the best indicator of the immediate state of immunologic competence and also the strongest predictor of the HIV-related complications in these patients. Cryptococcal meningitis was one of the AIDS defining illness in patients with a CD4 count which was less than 100/ml [21.] In one study (20), the average CD4 lymphocyte count in patients with AIDS and cryptococcosis was 46 cells/μl.The median CD4 cell count in this case series was 59.55 cells/μl.

Conclusion

In conclusion, the present study demonstrated the prevalence of cryptococcal meningitis only in immunocompromised individuals. It had an acute to a sub-acute presentation in a majority of the patients. The frank meningeal signs were less common in the isolated cryptococcal meningitis cases. Infection with HIV continues to be the most important predisposing factor for the development of CNS cryptococcosis, followed by chronic smoking, diabetes mellitus and prolonged steroid therapy. The occurrence of meningitis in patients with the HIV infection was most frequently due to opportunistic infections. The biotype which was responsible for cryptococcal meningitis in and around Bellary was C.neoformans var.neoformans. Cryptococcal meningitis was the AIDS defining illness in 50% of the patients. Cryptococcal infection remains the major opportunistic infection in HIV-infected patients with a CD4 cell count of <100 cells/μl. A high index of clinical suspicion and mycological surveillance is required to help in an early diagnosis and appropriate therapy.

References

1.
Dharmshale SN, Patil SA, Chowdhary A, Oberoi C. Disseminated cryptococcosis with extensive cutaneous involvement in AIDS. Ind J Med Microbiol 2006; (24)3:228-30.
2.
Currie BP and Casadevall A. Estimation of the prevalence of cryptococcal infection among patients infected with the human immunodeficiency virus in New york city. Clin Infect Dis 1994; 19:1029-33.
3.
Sullivan D, Haynes K, Moran G, Shanley D and Coleman D. Persistence, replacement and microevolution of Cryptococcus neoformans strains in recurrent meningitis in AIDS patients. J Clin Microbiol July1996; 34(7): 1739-17.
4.
Dismukes WE. Cryptococcal meningitis in patients with AIDS. J Infect Dis April 1988; 157(4):624-28.
5.
Chuck SL, MD and Sande MA, MD. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome.The New England Journal of Medicine Sept 21 1989;321(12): 794-99.
6.
Forbes BA, Daniel FS, Alice S. Procedure 53.13.Laboratory methods in basic mycology. In: Bailey and Scott’s Diagnostic Microbiology.11th edition.Philadelphia: Mosby publications 2004: 711-97.
7.
Forbes BA, Daniel FS, Alice S. Procedure 53.14.Laboratory methods in basic mycology. In: Bailey and Scott’s Diagnostic Microbiology.11th edition. Philadelphia: Mosby publications 2004: 711-97.
8.
Jagdish chander. Appendix A, Fungal culture media. In: A Text book of Medical mycology. 2nd edition. Interprint publishers: 376-80.
9.
Kyung J, Kwon-chung, Itzhack polacheck and John E. Bennett. Improved diagnostic Medium for Separation of Cryptococcus neoformans var. neoformans (Serotypes A and D) and Cryptococcus neoformans var. gattii (Serotypes B and C). J Clin Microbiol Mar1982; 15(3): 535-37.
10.
Lakshmi V, Sudha T, Teja VD, Umbala P. Prevalence of central nervous system cryptococcosis in human immunodeficiency virus reactive hospitalized patients. Ind J Med Microbiol 2007;25(2):146-9.
11.
Wadhwa A, Kaur R, Agarwal SK, Jain S, Bhalla P. AIDS – related opportunistic mycoses seen in a tertiary care hospital in North India. J Med Microbiol 2007; 56:1101-06.
12.
Ayyagiri A, Sharma AK, Prasad KN, Dhole TN, Kishore J and Chaudhary G. Spectrum of opportunistic infections in human immunodeficiency virus (HIV) infected cases in a tertiary care hospital. Indian J Med Microbiol 1999; 17(2) : 78-80.
13.
Bogaerts J, Rouvroy D, Taelman H, Kagame A, Aziz MA, Swinne D, et al. AIDS associated cryptococcal meningitis in Rwanda (1983-1992): Epidemiologic and diagnostic features. J Infect Dis 1999; 39: 32-7.
14.
Bava AJ, Negroni R, Arechavala A, Robles AM and Bianchi M. Cryptococcosis associated with AIDS in the Muniz hospital of Buenos Aires. Mycopathologia 1997;140:13-17.
15.
Kumarasamy N, Solomon S, Flanigan TP, Hemalatha R, Thyagarajan SP, Mayer KH. Natural history of human immunodeficiency virus disease in southern India. Clin Infect Dis 2003;36:79-85.
16.
Sobhani R, Basavaraj A, Gupta A, Bhave AS, Kadam DB, Sangle SA, et al. Mortality & clinical characteristics of hospitalized adult patients with HIV in Pune, India. Indian J Med Res 2007;126:116-21.
17.
Perfect JR, Casadevall A. Cryptococcosis. Infect Dis Clin North Am 2002;16:837-74.
18.
Saag MS, Graybill RJ, Larsen RA, Pappas PG, Perfect JR, Powderly WG, et al. Practice guidelines for the management of cryptococcal disease: Infectious Diseases Society of America. Clin Infect Dis 2000;30:710-8.
19.
Imwidthaya P, Poungvarin N. Cryptococcosis in AIDS. Postgrad Med J 2000;76: 85-88.
20.
Darras-Joly C, Chevret S, Wolff M, Matheron S, Longuet P, Casalino E, et al. Cryptococcus neoformans infection in France: epidemiologic features of and early prognostic parameters for 76 patients who were infected with human immunodeficiency virus. Clin Infect Dis 1996 Aug; 23(2):369-76.
21.
Thakur R, Sarma S, Kushwaha S. Prevalence of HIV associate cryptococcal meningitis and utility of microbiological determinants for its diagnosis in a tertiary care center. Ind J Pathol Microbiol April-June 2008; 51(2):212-14.

DOI and Others

DOI: JCDR/2012/3959:1989

DECLARATI ON ON COMPETING INTERESTS:
No competing Interests.


Date of Submission: Aug 23, 2011
Date of Peer Review: Oct 15, 2011
Date of Acceptance: Mar 10, 2012
Date of Publishing: May 01, 2012

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