Advancing the Understanding and Diagnosis of Histoplasmosis: Insights from a Tertiary Care Hospital in India

doi:10.21203/rs.3.rs-4891524/v1

Download PDF

Research Article

Advancing the Understanding and Diagnosis of Histoplasmosis: Insights from a Tertiary Care Hospital in India

https://doi.org/10.21203/rs.3.rs-4891524/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background

Histoplasma capsulatum, a dimorphic fungus, is a significant cause of endemic mycosis, particularly in immunocompromised individuals. While considered endemic to the Gangetic Plains in India, reports from nonendemic regions have been increasing. This study aims to enhance the understanding and diagnosis of histoplasmosis by describing cases from a tertiary care hospital in New Delhi, India.

Methods

A retrospective study involving adult patients diagnosed with histoplasmosis was conducted at Sir Ganga Ram Hospital, New Delhi, India, from July 2019 to March 2024. Clinical data were extracted from the hospital’s electronic medical records and analysed via SPSS software.

Results

Eleven patients with a mean age of 48.4 years were identified. The majority were male (90.9%) and had risk factors such as immunosuppressive therapy, HIV (human immunodeficiency virus) and diabetes. Common symptoms included fever (90.9%) and weight loss (72.7%). Hematological abnormalities such as anemia and leukopenia (36.3%) and radiological findings of splenomegaly (72.7%) and hepatomegaly (63.6%) were most common. Complications such as hemophagocytic lymphohistiocytosis (HLH) and multiple organ dysfunction syndrome (MODS) occurred in 27.2% of patients, with a mortality rate of 18.18%.

Discussion

Histoplasmosis often mimics tuberculosis (TB) in terms of symptoms and radiological findings, complicating its diagnosis in regions with high TB burdens. Immunosuppressive therapy, HIV, and diabetes are significant risk factors. Clinical presentations vary, including fever, weight loss, and uncommon manifestations like gastrointestinal (GI) and central nervous system (CNS) involvement, posing diagnostic challenges. Unlike those in the western literature, all patients in our study had disseminated histoplasmosis, suggesting the underdiagnosis of milder forms in India. Most patients respond well to intravenous L-AmB (liposomal amphotericin-B) followed by oral itraconazole, although complications such as HLH and MODS are common. The mortality rate was 18.18%, emphasizing the need for timely diagnosis and treatment.

Conclusion

This study reinforces the importance of heightened clinical suspicion and awareness for diagnosing histoplasmosis. Improved diagnostics with rapid and reliable tests are essential for better patient management and outcomes. Public health strategies should focus on educating healthcare providers about diverse presentations and mandating case notifications. An enhanced understanding of histoplasmosis can mitigate misdiagnosis rates and improve treatment outcomes.

Histoplasmosis

Granulomatous infection

Endemic mycosis

Tuberculosis mimic

Adrenal histoplasmosis

Histoplasma capsulatum

Invasive fungal infection

Amphotericin B

Itraconazole.

Histoplasma capsulatum, a dimorphic fungus, is distributed worldwide in localized areas of endemicity notably associated with river valleys. This soil-based fungus releases airborne conidia that can be inhaled.¹ The clinical spectrum spans from largely asymptomatic acute pulmonary disease to potentially fatal progressive disseminated disease if left untreated. It is the leading endemic mycosis in the United States and has gained global significance with the AIDS (acquired immunodeficiency syndrome) pandemic, increased intercontinental travel, and immunosuppressive medication usage.² In India, it is considered endemic in regions along the Gangetic Plain, such as West Bengal and Uttar Pradesh; however, the trend of reporting histoplasmosis cases has notably increased in recent years from nonendemic regions as well, which might be caused by increased awareness among clinicians to diagnose histoplasmosis.^3,4 However, it is frequently misdiagnosed as TB in countries with a high TB burden, and its clinicoradiological resemblance further complicates its diagnosis. A complete understanding of histoplasma endemicity and clinical presentation is crucial to increase the ability of clinicians to diagnose histoplasmosis. We describe 11 patients with histoplasmosis over a period of ~ 5 years from a single tertiary care hospital in New Delhi, India.

A retrospective observational study was conducted at the Department of Internal Medicine, Sir Ganga Ram Hospital, New Delhi, India, from July 2019 to March 2024, following ethical clearance from the institutional review board. The study involved adult patients diagnosed with histoplasmosis, confirmed by the presence of H. capsulatum in clinical specimens through histopathology or culture. Patients under 18 years of age were excluded.

Baseline demographic characteristics, underlying comorbidities, clinical presentation, organ involvement, method of diagnosis, treatment received, complications, and clinical outcomes were collected for each patient.

Clinical data were extracted from the hospital’s electronic medical records system and analysed via descriptive statistics. Numerical data were represented by means and standard deviations when applicable, whereas categorical variables were summarized by counts and percentages. SPSS statistical software was used for data analysis.

A total of 11 cases of histoplasmosis confirmed by histopathological examination of clinical specimens were included in the study. The mean (SD) age of the patients was 48.4 (25.1) years, with ages ranging from 20–70 years. Among the 11 patients, 10 (90.9%) were male, and 1 (9.1%) was female. Among these patients, 10 (90.9%) were male, and 1 (9.1%) was female. Notably, 10 patients (90.9%) had underlying risk factors, primarily the use of immunosuppressants such as tacrolimus, steroids, and methotrexate, whereas 1 patient (9.09%) had no identifiable risk factors (Table 1, Fig. 1).

Table 1

Baseline characteristics of 11 patients with histoplasmosis
Patient	Age (Years)	Gender	State of residence	Occupation	Underlying disease and risk factor
1	20	Male	Delhi	Farmer	Post renal transplant-immunosuppressants (tacrolimus and steroids)
2	44	Male	Delhi	Private sector employee	Post renal transplant- immunosuppressants (tacrolimus and steroids)
3	70	Female	Uttar Pradesh	Housemaker	Rheumatoid arthritis-immunosuppressants (Methotrexate)
4	39	Male	Uttar Pradesh	Tour guide	Ulcerative colitis- on steroids and azathioprine
5	65	Male	Bihar	Farmer	Diabetes Mellitus
6	35	Male	Uttarakhand	Businessman	HIV
7	58	Male	Haryana	Farmer	Nil
8	70	Male	Haryana	Businessman	Diabetes Mellitus chronic kidney disease
9	37	Male	Delhi	Businessman	HIV
10	62	Male	Uttar Pradesh	Businessman	Myasthenia gravis- on steroids
11	33	Male	Haryana	Farmer	HIV

The most common symptom was fever, which was observed in 10 patients (90.9%), followed by weight loss in 8 patients (72.7%). Generalized weakness was observed in 5 patients (45.4%) (Fig. 2).

Anaemia and leukopenia were the most common haematological abnormalities and were found in 4 patients (36.3%) each. The most prevalent radiological findings were splenomegaly, which was observed in 8 patients (72.7%), and hepatomegaly, which was noted in 7 patients (63.6%) (Table 2). A urinary histoplasma antigen test was performed in 4 patients, one of whom had a negative result.

Table 2

Laboratory and radiological parameters of 11 patients with histoplasmosis
Investigation	Number = 11 (%)
Hemoglobin (< 10 g/dl)	4 (36.3%)
TLC (< 4thous/ul)	4 (36.3%)
Platelet (< 100 thous/ul)	2 (18.1%)
Sodium (< 130 mmol/L)	2 (18.1%)
Radiological finding	Number = 11 (%)
Hepatomegaly	7 (63.6%)
Splenomegaly	8 (72.7%)
Lymphadenopathy	4 (36.3%)
Bilateral adrenal enlargement	2 (18.1%)
Pulmonary nodules	3 (27.2%)
Pleural thickening	1 (9.09%)
Right thalamic space-occupying lesion	1 (9.09%)
Liver lesion	1 (9.09%)

Diagnosis was made via histopathological examination of various tissue samples on the basis of various clinical presentations, which revealed the presence of intracellular budding yeast cells highlighted by Gomori methenamine silver stain (Fig. 3).

The majority (90.9%) of the patients received an initial intravenous course of intravenous L-AmB for 3 weeks followed by oral itraconazole therapy. HLH and MODS each developed in 3 patients (27.2%). One of the patients died even before the histopathological diagnosis of histoplasmosis could be made, while one patient expired while on initial L-AmB therapy (Fig. 4).

In our study, we describe 11 cases of histoplasmosis over a period of ~ 5 years from a single tertiary care center in New Delhi, India. Histoplasmosis, caused by the dimorphic fungus Histoplasma capsulatum, is a granulomatous infection that can affect multiple organs. While this fungus is found worldwide, it is more prevalent in North and Central America, parts of Asia, and Africa.¹

Randhawa and Gugnani's study forms the basis for understanding histoplasmosis in India, identifying 426 cases from 1954-2018.² The only evidence of the environmental source of Histoplasma in India was its isolation from soil near bat habitats in the Ganga River basin.⁵ In 1954, Panja and Sen documented the first case of disseminated histoplasmosis from Calcutta.⁶ Although it is considered endemic to the Gangetic Plain, cases have been reported nationwide. Most of the data on histoplasmosis in India come from case reports and series from centers in endemic regions.^7–10 Despite cases reported in South India, most patients are from northeastern endemic areas seeking treatment in southern India.¹¹ However, the trend of reporting histoplasmosis cases has notably increased in recent years from nonendemic regions.^12–16 In our study, all the patients belonged to the Gangetic Plain. However, this may be due to a referral bias given our hospital's substantial influx of patients from these states.

Only two patients in our study recalled exposure to birds. Given that sporadic cases account for approximately 95% of instances, many individuals with histoplasmosis may not recall exposure to bird or bat droppings.¹⁷ This is a significant consideration for clinicians assessing patients with symptoms suggestive of histoplasmosis.

In our study, most patients were receiving immunosuppressive therapy (n = 5, 45.4%), and three patients were HIV positive. Rozaliyani A et al. reviewed HIV status in 136 out of 207 histoplasmosis patients in India from 2018–2020 and reported that 91% were HIV-negative. Among these patients, diabetes was the most common risk factor.⁴ In our study, two patients had uncontrolled diabetes. With the increase in the diabetic population in India, this has become a significant emerging risk factor from an Indian perspective. We also report 2 patients who received immunosuppressants, namely, tacrolimus and steroids, for renal transplantation. Despite the elevated risk, posttransplant histoplasmosis remains rare, with an estimated incidence of less than 1%, even in endemic areas.^18,19 According to the Western data, most infections occurred within the initial 1–2 years following transplantation, a trend that we also observed in our study.²⁰

Histoplasmosis can present in various forms: asymptomatic (the most common), acute pulmonary (characterized by flu-like symptoms and often self-limiting), chronic pulmonary (resembling tuberculosis with chronic cough and chest pain) and disseminated (the rarest).²¹ This broad spectrum of manifestations can pose challenges in identifying histoplasmosis. Fever, weight loss, and generalized weakness are common presenting symptoms in Indian studies, which is consistent with our findings.^7,8,15 However, our study differs from a recent review by Benedict K et al. on histoplasmosis in the U.S., which revealed acute pulmonary histoplasmosis to be the most common form with more frequent pulmonary symptoms.¹⁷

The presentation of pulmonary histoplasmosis is similar to that of other common causes of pneumonia. However, certain symptoms and conditions, such as night sweats, lymphadenopathy, and pulmonary nodules, are particularly indicative of histoplasmosis.²² In our study, one patient with a pulmonary nodule succumbed to hemorrhagic shock after lung biopsy. The substantial mortality risk associated with lung biopsies underscores the genuine public health implications of histoplasma-related pulmonary nodules. These nodules often resemble lung cancer on imaging, resulting in unnecessary, costly, and invasive procedures. Further research on noninvasive methods to differentiate histoplasmosis-related pulmonary findings is needed. Pleural effusions occur in 1–5.7% of acute histoplasmosis patients, with some developing pleural fibrosis.^23,24 The postrenal transplant patient in our study presented with a cough and right-sided chest pain. FDG-avid right pleural thickening and underlying pleural effusion were identified, and histopathological examination of the pleural biopsy confirmed histoplasmosis.

Gastrointestinal (GI) histoplasmosis is rare in immunocompetent hosts, accounting for only 0.05% of cases.²⁵ In our study, two HIV-positive patients had GI histoplasmosis. One patient presented with subacute intestinal obstruction, while the other had loose stools. Both patients exhibited colonic ulceration on colonoscopy, along with circumferential thickening, which contributed to obstruction in one patient. These findings mimic various other conditions, such as tuberculosis, lymphoma, Crohn's disease, and malignancy. Both patients initially received empirical antitubercular therapy on the basis of their clinicoradiological profile. The need for invasive biopsy complicates the diagnosis of GI histoplasmosis, particularly in patients with isolated GI involvement, as in both cases.

Adrenal involvement in histoplasmosis has been reported in 30–40% of cases in clinical studies conducted globally, reaching 80% in autopsy series.^26,27 The rich vascularity and high local glucocorticoid concentration in the adrenal glands may explain this propensity. An Indian study by Singh M et al. revealed that 42.5% of patients had diabetes mellitus and were immunocompetent, which is consistent with other studies that reported adrenal involvement in immunocompetent hosts.^10,11,28 Our study reports two immunocompetent male patients with adrenal histoplasmosis who had diabetes and presented with adrenal insufficiency.

CNS histoplasmosis is rare, with data typically found in case reports and reviews.^29,30 While more common in immunocompromised patients, sporadic cases in immunocompetent individuals and cases of isolated CNS involvement have been documented.^31,32 Our study presents a case of isolated CNS histoplasmosis in an HIV patient who presented with hemiparesis and upper motor neuron facial palsy, with MRI (magnetic resonance imaging) showing a space-occupying lesion in the thalamus and caudate nucleus. A stereotactic brain biopsy confirmed histoplasmosis. The varied clinical manifestations and diagnostic challenges contribute to low clinical suspicion, as focal brain lesions such as abscesses or histoplasmomas are uncommon.³³

The diagnosis of histoplasmosis is complex and influenced by clinical syndromes and immune status and relies on culture, pathology, antigen/antibody testing, and polymerase chain reaction. Culturing of Histoplasma from clinical samples is the gold standard, with bone marrow or blood cultures preferred for disseminated disease, resulting in ~ 75% sensitivity.³⁴ However, cultures take at least four weeks to grow, limiting their clinical utility. On direct visualization, Histoplasma capsulatum var. capsulatum yeast appears ovoid and 2–4 µM in size, whereas var. duboisii are larger, generally 6–12 µM. These rapid and cost-effective tests are widely used globally, with sensitivity improving in advanced HIV patients due to a greater fungal burden.^34,35

Various antibody tests, including immunodiffusion, complement fixation, and enzyme immunoassays, are available. Immunodiffusion is less sensitive (~ 80%) but more specific than complement fixation is, especially for disseminated infections.³⁶ Antibody testing is more sensitive for subacute and chronic pulmonary histoplasmosis but less reliable for acute pulmonary histoplasmosis and early disseminated disease because of delayed antibody development.³⁷

Antigen detection has revolutionized the diagnosis of disseminated histoplasmosis, especially in urine samples.³⁸ The latest world health organization guidelines recommend diagnosing disseminated histoplasmosis in PLHA (people living with HIV) by detecting circulating histoplasma antigens.³⁹ Initially, limited to MiraVista Diagnostics in the United states, IMMY (Norman, OK, USA) developed the first commercial Histoplasma antigen detection test usable outside the USA.³⁷ The IMMY ALPHA ELISA (enzyme-linked immunosorbent assay) kit, validated in urine samples in 2007, and the IMMY Clarus assay, which is based on monoclonal antibodies, show improved sensitivity (95%).⁴⁰ Current antigen tests are mainly lab-based, with limited point-of-care capabilities and cross-reactivity.

Rapid lateral flow assays (LFAs) are in development, with MiraVista’s LFA showing excellent performance comparable to that of IMMY Clarus EIA.⁴¹ These LFAs need to be widely accessible and affordable worldwide for point-of-care diagnosis. Cross-reactivity with other fungi remains a significant challenge. A recent study by Puerta-Arias et al. described Hc670_Ag and Hc212_Ag specific for H. capsulatum as potential antigens, which requires further evaluation for sensitivity and specificity.⁴²

On imaging, pulmonary histoplasmosis can mimic other infections, inflammation, or tumors. Common Computed tomography (CT) findings include nodular opacities, consolidations, and ground-glass opacities. Solitary pulmonary nodules with or without calcifications, known as histoplasmomas, are common in endemic areas. Acute histoplasmosis may cause enlarged mediastinal and hilar lymph nodes, mimicking malignancy. Chronic pulmonary histoplasmosis typically affects the upper lung lobes with consolidation and cavitation, whereas disseminated histoplasmosis often presents with diffuse micronodules, which can be confused with miliary tuberculosis or metastases.⁴³

Disseminated histoplasmosis is a major cause of HLH in HIV patients, with no established treatment protocols, leading to mortality rates of 30–45%.^44,45 In a recent review of HLH in histoplasmosis, 65 out of 128 patients (50.8%) were HIV-infected, 20 (15.6%) had rheumatic disease, 15 (11.7%) had organ transplants, and three (2.3%) had hematologic malignancies.⁴⁶ In our study, HLH developed in three patients, two postrenal transplant recipients and one patient with rheumatoid arthritis, with no mortality.

In 2007, the IDSA (Infectious diseases society of America) guidelines outlined histoplasmosis treatment. Acute pulmonary infections (< 4 weeks) may not require treatment; persistent symptoms may require a 3-month itraconazole course. Noncavitary chronic pulmonary histoplasmosis requires six months of therapy, whereas cavitary disease requires up to a year. Progressive disseminated histoplasmosis requires amphotericin-B for 2–4 weeks followed by itraconazole for one year. The use of L-AmB leads to better outcomes. Posaconazole is used as salvage therapy but is not formally recommended by the IDSA.¹ A recent trial led by Pasqualotto AC et al. reported that one-day induction therapy with 10 mg/kg L-AmB was safe for treating AIDS-related histoplasmosis, but further phase III clinical trials are necessary to confirm its efficacy compared with that of standard L-AmB therapy.⁴⁷

Limitations- As this was a retrospective study, the number of patients included was relatively small, and the data were sourced from a single center.

The lack of epidemiological knowledge is one of the key factors in diagnostic delays, underscoring the need for public health system strategies, such as compulsory histoplasmosis notification, as implemented in Brazil in 2021, to heighten suspicion in nonendemic areas.⁴⁸

An improved understanding of histoplasmosis and prevention efforts require improved epidemiological data, which, in turn, require faster and more reliable diagnostic tests, as well as clearer guidance for healthcare providers about which tests to use and which patients to test. Increased suspicion, enhanced diagnostics, and routine fungal infection screening in TB-endemic regions can mitigate misdiagnosis rates and improve patient outcomes.

Acquired immunodeficiency syndrome (AIDS)
Central nervous system (CNS)
Computed tomography (CT)
Enzyme-linked immunosorbent assay (ELISA)
Gastrointestinal (GI)
Hemophagocytic lymphohistiocytosis (HLH)
Human immunodeficiency virus (HIV)
Infectious Diseases Society of America (IDSA)
Liposomal amphotericin-B (L-AmB)
Lateral flow assays (LFA)
Magnetic resonance imaging (MRI)
Multiple organ dysfunction syndrome (MODS)
People living with HIV (PLHA)

Tuberculosis (TB)

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Sir Ganga Ram Hospital (Approval No: EC/04/24/2496). Given the retrospective nature of the study, a waiver of consent was granted by the committee.

Consent for publication

Not applicable

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

No, I declare that the authors have no competing interests as defined by BMC, or other interests that might be perceived to influence the results and/or discussion reported in this paper.

Funding

This research received no specific grant from any funding agency.

Authors' contributions

All authors contributed to the study's design, data collection, and analysis. J.S. drafted the main manuscript. All authors reviewed, edited, and approved the final version of the manuscript.

Acknowledgements

Not applicable

Akram Akram SM, Koirala J. Histoplasmosis. 2023 Aug 8. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024.
Bahr NC, Antinori S, Wheat LJ, Sarosi GA. Histoplasmosis infections worldwide: thinking outside of the Ohio River valley. Curr Trop Med Rep. 2015; 2:70–80.
Randhawa HS, Gugnani H. Occurrence of Histoplasmosis in the Indian Sub-Continent: An Overview and Update. 2018; 7:71-83.
Rozaliyani A, Setianingrum F. The Review of Histoplasmosis Endemicity and Current Status in Asia. Histoplasma and Histoplasmosis. IntechOpen; 2020.
Sanyal M, Thammayya A. Histoplasma capsulatum in the soil of Gangetic Plain in India. The Indian Journal of Medical Research. 1975; 63:1020-1028
Panja G, Sen S. A unique case of histoplasmosis. J Indian Med Assoc 1954; 23:257–8.
Gopalakrishnan R, Nambi PS, Ramasubramanian V, Abdul Ghafur K, Parameswaran A. Histoplasmosis in India: truly uncommon or uncommonly recognised? J Assoc Physicians India. 2012; 60:25-8.
Bhattacharyya K, Pal S, Dutta A, Bhattachryya PP, Laskar S. Histoplasmosis of Adrenal Gland: A 5 Years' Review from a Multispecialty Diagnostic Centre. J Lab Physicians. 2022; 15:243-252.
Agrawal SS, Chakraborty PP, Sinha A, Maiti A, Chakraborty M. ADRENAL HISTOPLASMOSIS: AN EASTERN INDIAN PERSPECTIVE. Acta Endocrinol (Buchar). 2022; 18:106-114.
Gupta A, Ghosh A, Singh G, Xess I. A Twenty-First-Century Perspective of Disseminated Histoplasmosis in India: Literature Review and Retrospective Analysis of Published and Unpublished Cases at a Tertiary Care Hospital in North India. Mycopathologia. 2017;182:1077-1093.
Deodhar D, Frenzen F, Rupali P, David D, Promila M, Ramya I, Seshadri MS. Disseminated histoplasmosis: a comparative study of the clinical features and outcome among immunocompromised and immunocompetent patients. Natl Med J India. 2013; 26:214-5.
Patel AK, Patel KK, Toshniwal H, Gohel S, Chakrabarti A. Histoplasmosis in non-endemic North-Western part of India. Indian J Med Microbiol. 2018; 36:61-64.
Samaddar A, Sharma A, Kumar Ph A, Srivastava S, Shrimali T, Gopalakrishnan M, Bohra GK. Disseminated histoplasmosis in immunocompetent patients from an arid zone in Western India: A case series. Med Mycol Case Rep. 2019; 25:49-52.
Mahajan VK, Raina RK, Singh S, Rashpa RS, Sood A, Chauhan PS, et al. Case Report: Histoplasmosis in Himachal Pradesh (India): An Emerging Endemic Focus. Am J Trop Med Hyg . 2017; 97:1749.
Arora N, Shukla S, Vijaykumar D, Suri V, Kumar R, Pannu AK. Pyrexia of unknown origin in HIV-negative adults from Himachal Pradesh (India): will you suspect disseminated histoplasmosis? Trop Doct. 2020; 50:275–7.
Rana A, Kotton CN, Mahapatra A, Nandwani A, Sethi S, Bansal SB. Post kidney transplant histoplasmosis: An under-recognized diagnosis in India. Transpl Infect Dis. 2021; 23: e13523.
Benedict K, Toda M, Jackson BR. Revising Conventional Wisdom About Histoplasmosis in the United States. Open Forum Infect Dis. 2021; 8: ofab306.
Cuellar-Rodriguez J, Avery RK, Lard M, Budev M, Gordon SM, Shrestha NK, et al. Histoplasmosis in solid organ transplant recipients: 10 years of experience at a large transplant center in an endemic area. Clin Infect Dis. 2009; 49:710–6.
Grim SA, Proia L, Miller R, Alhyraba M, Costas-Chavarri A, Oberholzer J, et al. A multicenter study of histoplasmosis and blastomycosis after solid organ transplantation. Transpl Infect Dis. 2012; 14:17–23.
Miller R, Assi M. Endemic fungal infections in solid organ transplant recipients-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019; 33: e13553.
Lin Blache J, Ryan K, and Arceneaux K. 2011. Histoplasmosis. Compend. Contin. Educ. Vet. 33: E1–E10, quiz E11.
Benedict K, Kobayashi M, Garg S, Chiller T, Jackson BR. Symptoms in Blastomycosis, Coccidioidomycosis, and Histoplasmosis Versus Other Respiratory Illnesses in Commercially Insured Adult Outpatients-United States, 2016-2017. Clin Infect Dis. 2021; 73: E4336–44.
Kilburn CD, McKinsey DS. Recurrent massive pleural effusion due to pleural, pericardial, and epicardial fibrosis in histoplasmosis. Chest. 1991; 100:1715–7.
Schub HM, Spivey CG, Baird GD. Pleural involvement in histoplasmosis. Am Rev Respir Dis. 1966; 94:225–32.
Zhu L, Zhang W, Yang L, Guo T, Su C, Yang J. Disseminated Histoplasmosis: Intestinal Multiple Ulcers without Gastrointestinal Symptoms in an Immune Competent Adult. J Cytol Histol. 2014; 5:231.
Goswami RP, Pramanik N, Banerjee D, Raza MM, Guha SK, Maiti PK. Histoplasmosis in eastern India: the tip of the iceberg? Trans R Soc Trop Med Hyg. 1999; 93:540–2.
Goodwin RA, Shapiro JL, Thurman GH, Thurman SS, Des Prez RM. Disseminated histoplasmosis: clinical and pathologic correlations. Medicine. 1980; 59:1–33.
Singh M, Chandy DD, Bharani T, Marak RSK, Yadav S, Dabadghao P, et al. Clinical outcomes and cortical reserve in adrenal histoplasmosis-A retrospective follow-up study of 40 patients. Clin Endocrinol (Oxf). 2019; 90:534–41.
Riddell J., Wheat L.J. Central Nervous System infection with Histoplasma capsulatum. J. Fungi. 2019; 5:70.
Saccente M, McDonnell RW, Baddour LM, Mathis MJ, Bradsher RW. Cerebral histoplasmosis in the azole era: report of four cases and review. South Med J. 2003; 96:410–6.
Ramireddy S, Wanger A, Ostrosky L. An instructive case of CNS histoplasmosis in an immunocompetent host. Med Mycol Case Rep. 2012; 1:69-71.
Schestatsky P., Chedid M.F., Amaral O.B., Unis G., Oliveira F.M., Severo L.C. Isolated central nervous system histoplasmosis in immunocompetent hosts: A series of 11 cases. Scand. J. Infect. Dis. 2006; 38:43–48.
Klein C.J., Dinapoli R.P., Temesgen Z., Meyer F.B. Central nervous system histoplasmosis mimicking a brain tumor: Difficulties in diagnosis and treatment. Mayo Clin. Proc. 1999; 74:803–807
Wheat L.J., Azar M.M., Bahr N.C., Spec A., Relich R.F., Hage C. Histoplasmosis. Infect. Dis. Clin. N. A. 2016; 30:207–227.
Kauffman C.A. Histoplasmosis: A clinical and laboratory update. Clin. Microbiol. Rev. 2007; 20:115–132.
Arango-Bustamante K., Restrepo A., Cano L.E., de Bedout C., Tobon A.M., Gonzalez A. Diagnostic value of culture and serological tests in the diagnosis of histoplasmosis in HIV and non-HIV Colombian patients. Am. J. Trop. Med. Hyg. 2013; 89:937–942.
Villareal K, Price A, Pasqualotto AC, Bahr NC. The Current and Future States of Diagnostic Tests for Histoplasmosis with a Focus on People with HIV and Disseminated Histoplasmosis. J Fungi (Basel). 2023; 9:793.
Falci D.R., Hoffmann E.R., Paskulin D.D., Pasqualotto A.C. Progressive disseminated histoplasmosis: A systematic review on the performance of non-culture-based diagnostic tests. Braz. J. Infect. Dis. 2017; 21:7–11.
Perez F, Caceres DH, Ford N, Ravasi G, Gomez BL, Pasqualotto AC, et al. Summary of Guidelines for Managing Histoplasmosis among People Living with HIV. J Fungi (Basel). 2021; 7:134.
Cáceres DH, Samayoa BE, Medina NG, Tobón AM, Guzmán BJ, Mercado D, et al. Multicenter Validation of Commercial Antigenuria Reagents To Diagnose Progressive Disseminated Histoplasmosis in People Living with HIV/AIDS in Two Latin American Countries. J Clin Microbiol. 2018;56:e01959-17.
Martínez-Gamboa A, Niembro-Ortega MD, Torres-González P, Santiago-Cruz J, Velázquez-Zavala NG, Rangel-Cordero A, et al. Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico. PLoS Negl Trop Dis. PLoS Neglected Trop. Dis. 2021;15: e0009215.
Puerta-Arias JD, Isaza Agudelo JP, Naranjo Preciado TW. Identification and production of novel potential pathogen-specific biomarkers for diagnosis of histoplasmosis. Microbiol Spectr. Microbiol Spectr 11: e00939-23.
Mango AL Di, Gomes ACP, Hochhegger B, Zanetti G, Marchiori E. Computed tomography findings of pulmonary histoplasmosis: pictorial essay. Radiol Bras. 2023; 56:162-167.
Tabaja H, Kanj A, El Zein S, Comba IY, Chehab O, Mahmood M. A Review of Hemophagocytic Lymphohistiocytosis in Patients With HIV. Open Forum Infect Dis 2022;9: ofac071.
Fazal F, Gupta N, Mittal A, Ray A. Haemophagocytic lymphohistiocytosis in human immunodeficiency virus: a systematic review of literature. Drug Discov Ther 2020; 14:226–31.
Chen H, Yuan Q, Hu H, Wang J, Yu M, Yang Q, et al. Hemophagocytic Lymphohistiocytosis Secondary to Disseminated Histoplasmosis in HIV Seronegative Patients: A Case Report and Review of the Literature. Front Cell Infect Microbiol. 2022; 12:847950.
Pasqualotto AC, Lana DD, Godoy CSM, Leitão TDMJS, Bay MB, Damasceno LS, et al. Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial. Clin Infect Dis. 2023; 77:1126-1132.
Paixão AG, Almeida MA, Correia RES, Kamiensky BB, Zancopé-Oliveira RM, Lazera M dos S, et al. Histoplasmosis at a Reference Center for Infectious Diseases in Southeast Brazil: Comparison between HIV-Positive and HIV-Negative Individuals. Trop Med Infect Dis. 2023; 8:271.

No competing interests reported.

Download PDF

Editorial decision: Revision requested
30 Sep, 2024
Reviews received at journal
30 Sep, 2024
Reviews received at journal
21 Sep, 2024
Reviews received at journal
11 Sep, 2024
Reviewers agreed at journal
08 Sep, 2024
Reviews received at journal
07 Sep, 2024
Reviewers agreed at journal
07 Sep, 2024
Reviewers agreed at journal
06 Sep, 2024
Reviewers agreed at journal
06 Sep, 2024
Reviewers agreed at journal
05 Sep, 2024
Reviewers invited by journal
05 Sep, 2024
Editor invited by journal
14 Aug, 2024
Editor assigned by journal
13 Aug, 2024
Submission checks completed at journal
13 Aug, 2024
First submitted to journal
10 Aug, 2024

You are reading this latest preprint version

Advancing the Understanding and Diagnosis of Histoplasmosis: Insights from a Tertiary Care Hospital in India

Status:

Version 1

Abstract

Figures

Background

Methods

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1