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"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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MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
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.
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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.
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Dr. Mamta Gupta
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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.
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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.
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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)
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.
On April 2011

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
On Jan 2020

Important Notice

Case Series
Year : 2024 | Month : May | Volume : 18 | Issue : 5 | Page : ER01 - ER03 Full Version

Incidentally Diagnosed Disseminated Histoplasmosis among Non HIV Patients: A Series of Three Cases with Review of Literature

Published: May 1, 2024 | DOI:
Priyanka Purohit, Nehal Minda, Navneet Bohra, Arshad Khan

1. Assistant Professor, Department of Pathology, Ananta Institute of Medical Sciences and Research Centre, Udaipur, Rajasthan, India. 2. Assistant Professor, Department of Pathology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India. 3. Assistant Professor, Department of Opthalmology, Ananta Institute of Medical Sciences and Research Centre, Udaipur, Rajasthan, India. 4. Senior Resident, Department of Radiology, Dr. Sampurnanand Medical College, Jodhpur, Rajasthan, India.

Correspondence Address :
Dr. Priyanka Purohit,
207, Jai Shree Krishna Residency, New Navratan, Udaipur-313001, Rajasthan, India.


Histoplasmosis is a rare airborne fungal infection that is soil-based and is mostly documented in Human Immunodeficiency Virus (HIV)-positive patients. It is common in people living near valley regions. Hereby, authors report three cases of Asian women from different regions of Southern Rajasthan who died due to delayed diagnosis of histoplasmosis within a few days of admission. They all had complaints of fatigue and fever for one month. One presented with decreased urine output and pancytopenia, while the others had complaints of prolonged fever with pancytopenia and fatigue. In all three cases, bone marrow examination was done, and they shared the same diagnosis - disseminated histoplasmosis. It was further confirmed by special stains and microbiological investigations. Authors also reviewed recent articles based on South Asian region histoplasmosis case reports and found three case presentations with the same clinical presentation and outcomes. Treatment was started, but patients deteriorated and died within 10 days of admission. Delay in the diagnosis of histoplasmosis leads to the death of patients. Therefore, histoplasmosis should be considered as a differential diagnosis for prolonged fever with pancytopenia and chronic infections.


Bone marrow, Diabetes, Pancytopenia, Special stains

Histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum. It has two types- Histoplasma capsulatum var. capsulatum and Histoplasma capsulatum var. duboisii, which can cause disease in humans (1). Histoplasmosis is defined according to the European Organisation for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) in 2008 (2). It is a disease in which Histoplasma species are found positive in any culture or confirmed by histopathology of blood, bone marrow, or any other infected sites. If a patient shows involvement at a single site and lacks symptoms or signs of systemic involvement, the disease is defined as focal histoplasmosis. To decrease the mortality rate due to histoplasmosis, early diagnosis of the disease should be conducted. Most infected individuals remain asymptomatic and do not get diagnosed with histoplasmosis, leading to fatal outcomes. Disseminated histoplasmosis is commonly observed in older and HIV-positive patients (3),(4),(5). Disseminated histoplasmosis is a diseased state where Histoplasma capsulatum is present in the blood and bone marrow or the fungus is confirmed from multiple normal sites in the organism (6),(7),(8). It is a common opportunistic infection in HIV-positive patients (9),(10). The time course of the infection in these patients is typically months, but if left untreated, it can be fatal. Authors hereby present three cases of Pyrexia of Unknown Origin (PUO) in 40-45-year-old females with common complaints of fatigue and pancytopenia residing in Southern Asia regions of India.

Case Report

Case 1

A 42-year-old female with a past medical history of Diabetes Mellitus type II and Hypertension for seven years was admitted to the hospital with complaints of decreased urine output, fatigue, diminished vision, and pedal swelling for 10 days. The patient had been on Insulin and other hypertensive medications for the last five years. She had a history of a single blood transfusion 17 days prior at a small centre due to weakness and shortness of breath, where 350 mL of whole blood was transfused. On physical examination, the patient appeared pale, had bilateral pedal swelling, an increased respiratory rate of 35, blood sugar level of 320 mg/dL, and blood pressure of 160/90 mmHg. Diabetic retinopathy was observed on ocular examination. Laboratory investigations from a complete blood count report revealed pancytopenia with a haemoglobin level of 5.8 g/dL, platelet count of 70,000/cumm, and total leukocyte count of 2000/cumm. Urine output was decreased and showed proteinuria with pus cells. Kidney function tests showed derangement with increased urea and creatinine levels of 270 mg/dL and 7 mg/dL, respectively. Liver function tests were normal, and other parameters were within normal limits. A chest X-ray showed normal findings, while an abdominal ultrasound revealed contracted kidneys with mild hepatosplenomegaly, which progressed to moderate splenomegaly in a repeat ultrasound done after three days.

In the following days, the patient started experiencing shortness of breath and altered sensorium. Cerebrospinal Fluid (CSF) analysis was performed, and it was normal. Peripheral smear showed morphologically normal findings with pancytopenia. Subsequently, a bone marrow examination was conducted, which revealed small budding intracellular yeast colonies exhibiting a “halo” effect around each organism and haematoxylinophilic nuclei stained with Haematoxylin and Eosin (H&E) stain. Periodic Acid Sciff (PAS) and Grocott-Gomori’s Methenamine Silver (GMS) stains were performed on bone marrow biopsy slides, showing positive intracellular colonies, confirming the presence of Histoplasma capsulatum in the bone marrow (Table/Fig 1),(Table/Fig 2),(Table/Fig 3). Therefore, the diagnosis of bone marrow infiltration by Histoplasma was established based on both aspiration and bone marrow biopsy. The patient underwent dialysis, and her creatinine levels improved, but her condition deteriorated, and she passed away within 10 days.

Case 2

A case of 69-year-old female who presented to the medicine Outpatient Department (OPD) with complaints of prolonged fever, shortness of breath, and fatigue lasting for one month. She was immunocompetent and did not had any other underlying illnesses such as HIV, diabetes, or hypertension. Upon examination and investigation, she was found to be pale, with an elevated respiratory rate. Her blood pressure and pulse were normal. The Complete Blood Count (CBC) report revealed pancytopenia with a haemoglobin level of 10 mg/dL, platelet count of 14,000/cumm, and total leukocyte count of 3000/cumm. Random blood sugar was 273 mg/dL, Lactate Dehydrogenase (LDH) was elevated to 200 U/L, and Dengue NS1 antigen was positive. All other parameters were within normal limits. Kidney function tests, liver function tests, procalcitonin levels, and urine examination were normal. Bone marrow aspiration and biopsy were performed due to pancytopenia, and both tests were positive for intracellular fungal elements in macrophages, confirming histoplasmosis.

On radiological investigations, the chest X-ray showed normal findings, while the ultrasound of the whole abdomen was unremarkable. A Computed Tomography (CT) scan of the brain revealed mild periventricular hyperdensity in the right parietal regions, possibly indicating soft calcifications. The patient was transferred to the Respiratory Intensive Care Unit (ICU) within two days, and her condition continued to deteriorate, and passed away within 10 days of admission. Meanwhile, she was being treated for dengue with steroids and fluid infusion as symptomatic treatment.

Case 3

Another case was reported during the same period at Jodhpur Government Hospital. A 48-year-old female presented with breathlessness, fever, and fatigue and was admitted to the ICU. All investigations were conducted, and the CBC revealed pancytopenia, along with an elevated LDH level of up to 300 IU/L. Her chest X-ray showed diffuse areas of involvement, but all other investigations were normal. She had a brief history of cough and breathlessness. Steroids were initiated to address the shortness of breath, but no improvement was observed.

On bone marrow examination, small budding intracellular yeast colonies were identified, displaying a “halo” effect around each organism and haematoxylinophilic nuclei stained with H&E stain. PAS and GMS stains were performed on bone marrow biopsy slides, showing positive intracellular colonies confirming the presence of Histoplasma capsulatum in the bone marrow, with the same morphology as the identified histoplasma. Subsequently, the patient developed seizures, prompting a suggested Magnetic Resonance Imaging (MRI) of the brain, the findings of which are explained below (Table/Fig 4),(Table/Fig 5),(Table/Fig 6),(Table/Fig 7). Antifungal therapy was initiated, resulting in an improvement in the CBC, but unfortunately, the patient passed away within two days. Once again, a delay in diagnosis and hesitation to administer antifungal therapy contributed to the patient’s death.


Three cases of histoplasmosis were reported in apparently immunocompetent individuals from the desert and arid zone in western Rajasthan, India. The patients presented with similar complaints of pancytopenia and weakness. None of them were initially diagnosed with disseminated histoplasmosis. Humans acquire this infection through the inhalation of microconidia of yeast. Most infected individuals also experience haematogenous spread of the organism to reticuloendothelial organs such as the liver, spleen, and bone marrow (4). A review study conducted in South Asia by Wang TL et al., on disseminated histoplasmosis noted that none of the reports initially considered histoplasmosis in the early diagnosis (11). First case was initially considered chronic kidney disease as the cause of bone marrow suppression leading to pancytopenia. Dialysis was performed, her renal status improved, but her clinical condition did not. She developed altered sensorium, breathlessness, anorexia, and her oxygen levels dropped. Subsequently, along with dialysis, her bone marrow work-up was initiated. On bone marrow examination, aspiration revealed the presence of intracellular yeast colonies with a “halo” effect inside macrophages, shown in (Table/Fig 1),(Table/Fig 2) known as the Haemophagocytosis phenomenon (12). The bone marrow biopsy showed fungal filaments, although histoplasmosis can be confused with Cryptococcus and Blastomyces dermatitidis, they can be differentiated based on the fact that cryptococci are carminophilic and Blastomyces cells are multinucleated, thick-walled, and bud from a base. The most important distinguishing feature is that only Histoplasma is PAS and GMS positive, as shown in (Table/Fig 3), while other fungi show a negative response to these special stains.

In first case, patient had a history of previous blood transfusions and i.v. iron transfusions at some small centre. When the diagnosis was made, liposomal Amphotericin B was advised to the patient, but unfortunately, the patient died. It is worth noting that the lungs remained normal until the end, and the infection spread rapidly throughout all tissues. Within 10 days of admission, the patient passed away. She developed moderate hepatosplenomegaly towards the end. If the diagnosis could have been made earlier, the patient might have been saved. Therefore, Histoplasmosis should be considered in the differential diagnosis among patients with chronic kidney disease along with any immunocompromised conditions (13). In India, the disease is endemic in the eastern part, with most cases reported in the Gangetic West Bengal (14). Other two patients also presented with the same complaints of fever and pancytopenia and were diagnosed with disseminated histoplasmosis.

Samaddar A and Sharma A concluded that diagnosing disseminated histoplasmosis at an early stage is very challenging due to its common symptoms, which are similar to other infectious diseases, especially in immunocompetent individuals, similar to present study (15). The fact that patients who do not visit endemic areas are contracting the disease is a point of concern, indicating that the western arid region of the Indian subcontinent is also becoming endemic to this disease. In another study by Kathuria S et al., it was reported that adrenal glands were the most commonly involved organs in disseminated histoplasmosis, followed by the liver, skin, spleen, lymph nodes, and bone marrow (16). Wang N et al., demonstrated that disseminated histoplasmosis infection can present with unexplained fever, and that metagenomics Next Generation Sequencing (mNGS) can be a valuable complement to bone marrow aspiration for diagnosing this disease, similar to index cases presenting with PUO (17). Therefore, PUO should definitely be evaluated for histoplasmosis in arid regions as well.


Patients with Histoplasma infection are predominantly women. There are no defined age and immune status criteria for this deadly infection. Therefore, patients presenting with prolonged fever and pancytopenia should be evaluated for Histoplasma infection regardless of the rarity and immune status of those affected. In all three cases of the above cases, the medical community failed to save the patients due to delayed diagnosis. Based on the epidemiological data of histoplasmosis in nearby valley regions, these cases challenge the notion that this infection is limited to humid areas, as they were reported in dry regions during the months of November to January. Disseminated histoplasmosis should be considered as a differential diagnosis in patients with chronic kidney disease presenting with pancytopenia and should be treated promptly to improve outcomes. This deadly disease does not discriminate based on age or timing of onset. Over the past few years, cases of disseminated histoplasmosis have been rapidly reported worldwide, despite endemic and geographical variations. However, more systematic and comprehensive studies are needed in this field to accurately estimate the true burden of histoplasmosis.


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DOI and Others

DOI: 10.7860/JCDR/2024/68252.19356

Date of Submission: Oct 24, 2023
Date of Peer Review: Dec 13, 2023
Date of Acceptance: Feb 26, 2024
Date of Publishing: May 01, 2024

Author declaration:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

• Plagiarism X-checker: Oct 25, 2023
• Manual Googling: Jan 24, 2024
• iThenticate Software: Feb 23, 2024 (11%)

Etymology: Author Origin

Emendations: 7

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