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  Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 36  |  Issue : 1  |  Page : 61-64
 

Histoplasmosis in non-endemic North-Western part of India


1 Infectious Diseases Clinic, “VEDANTA” Institute of Medical Sciences, Ahmedabad, Gujarat, India
2 Infectious Diseases and Tropical Medicine Clinic, Ahmedabad, Gujarat, India
3 Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication2-May-2018

Correspondence Address:
Dr. Arunaloke Chakrabarti
Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmm.IJMM_18_12

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 ~ Abstract 

Purpose of Study: The western and North-Western parts of India are usually considered non-endemic for histoplasmosis. On the contrary, we observe histoplasmosis cases with relatively higher frequency from this region although the awareness and laboratory facility to diagnose the disease are not adequate. Hence, we planned the present retrospective study to compile the cases and to analyse different clinical parameters. Materials and Methods: Medical records of the patients diagnosed with histoplasmosis during January 2012–August 2017 at two infectious disease clinics of Ahmedabad were included in this study. Results: During the study, 12 cases of histoplasmosis were diagnosed. The median age of the patients was 53 years; all males except one. The diagnosis of histoplasmosis was confirmed on histopathology for 11 cases, and one patient was diagnosed as probable histoplasmosis. The patients were either from Gujarat or Rajasthan without any travel history to endemic zone of histoplasmosis, except one patient. The majority (67%) of the patients had no apparent immunosuppression. Adrenal enlargement, oral ulcers and lymphadenopathy were common presentations in four patients each. We lost two patients in follow-up, and rest 10 patients responded to either to amphotericin B deoxycholate and/or itraconazole therapy. Conclusion: This study highlights that Gujarat and Rajasthan are an endemic region for histoplasmosis, and a systematic study is required to understand epidemiology of the disease. Histoplasmosis should be a differential diagnosis in a patient presenting with adrenal enlargement, lymphadenopathy, oral ulcers and fever of unknown origin in this region.


Keywords: Epidemiology, galactomannan, histoplasmosis, itraconazole, therapy


How to cite this article:
Patel AK, Patel KK, Toshniwal H, Gohel S, Chakrabarti A. Histoplasmosis in non-endemic North-Western part of India. Indian J Med Microbiol 2018;36:61-4

How to cite this URL:
Patel AK, Patel KK, Toshniwal H, Gohel S, Chakrabarti A. Histoplasmosis in non-endemic North-Western part of India. Indian J Med Microbiol [serial online] 2018 [cited 2018 Jul 20];36:61-4. Available from: http://www.ijmm.org/text.asp?2018/36/1/61/231681



 ~ Introduction Top


Histoplasmosis, caused by dimorhphic fungus, Histoplasma capsulatum is known to be endemic in certain geographical regions of India including Assam, Bihar, Delhi, Haryana, Punjab, Uttar Pradesh and West Bengal, though occasional cases were reported from nearly every corner of the country since AIDS epidemic.[1] Case series or sporadic cases had been reported from South India, but the majority of those patients were resident of Northeastern part of the country and visited South India for treatment of their ailments.[2] Western and North-Western parts of India were never considered as an endemic zone for histoplasmosis, as cases are reported rarely. Only six patients with histoplasmosis were reported from this region till date.[3],[4],[5],[6],[7],[8],[9] The clinicians of this region do not suspect or attempt to diagnose histoplasmosis although the disease is great mimicker of tuberculosis, which is highly prevalent in this region. Histoplasma antigen detection, a test that helps in diagnosis of histoplasmosis with minimal invasive procedure, is not available in the laboratories of this region. We describe here 12 patients with histoplasmosis over relatively short period (~5.5 years) from two tertiary care infectious disease clinics of Ahmedabad and highlight the possibility of missing histoplasmosis cases in this so-called non-endemic zone.


 ~ Materials and Methods Top


This is a retrospective study by inclusion of cases diagnosed as histoplasmosis during January 2012–August 2017 at two tertiary care infectious disease clinics (ID Clinic and IDTM clinic) at Ahmedabad, Gujarat with average daily outdoor patient burden of 75/day. The study was approved by the respective Ethics Committee of the two ID clinics.

Diagnosis of histoplasmosis: patients samples were collected from different sites depending on the site of lesion, for example, lymph node, mucosa, skin nodule, lung or adrenal gland. The diagnosis of histoplasmosis was confirmed by the presence of budding yeast cells in the histiocytes on histopathology. In one patient, probable histoplasmosis was diagnosed, as the patient presented with fever of unknown origin with adrenal enlargement, raised serum galactomannan (1.67 index) (Platelia™ Aspergillus EIA, Bio-Rad, France), no other tests suggesting alternative diagnosis and the patient responded to itraconazole therapy.

The demographics, place of stay, travel history, underlying illness and comorbidities, site of infection, treatment and outcome history of all patients with histoplasmosis were recorded.


 ~ Results Top


A total of 12 patients were diagnosed for histoplasmosis at the two clinics during the study; 11 patients were diagnosed by histopathological examination showing the presence of budding yeast cells (2–4 μm) in the histiocytes with pseudocapsule on histopathology [Figure 1]. Rest one patient was diagnosed as probable histoplasmosis, as she presented with fever of unknown origin with right adrenal enlargement on PET CT and without any radiological evidence of suggesting tuberculosis anywhere in body; serum galactomannan (1.67 index) was positive, and she responded clinically with fall of galactomannan level after 6 months itraconazole therapy. CT guided endoscopic adrenal biopsy was technically difficult in that patient.
Figure 1: Transbronchial Lung Biopsy showing many intracellular yeast consistent with histoplasmosis; (1a) Haematoxylin and Eosin stained and (1b) Gomori methenamine silver stained

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The demographic features, site involved, underlying disease, mode of diagnosis, treatment and outcome of those cases are described in [Table 1]. The median age of the patients was 53 years with range 34–76 years; except one, all were males. Of those 12 patients, seven were resident of Gujarat and rest five were from Rajasthan. The places of origin of the patients are detailed in [Table 1] and [Figure 2]. Except one patient, none of those patients had travel history to any endemic area. The patient residing at Jaipur had an extensive travel history to Thailand, Vietnam and South Korea. He was HIV positive also. Adrenal enlargement, oral ulcers and lymphadenopathy were noted in four patients each, and two had pulmonary nodule. Two patients had extensive cutaneous disease, and one had nasolabial ulcerative lesion with palatal ulcer [Figure 3] and [Figure 4]. The patient number 11 had slowly progressive skin nodules over both sides of face and forehead and developed hoarseness of voice. Indirect laryngoscopy showed granulomatous lesion over left vocal cord and biopsy of the lesion confirmed histoplasmosis. Only two patients were HIV positive and two received immunosuppressive therapy for autoimmune hepatitis and systemic lupus erythematosus; rest eight patients were apparently immunocompetent though five of those patients had diabetes. Two patients were lost during follow-up and rest 10 patients responded either to amphotericin B deoxycholate and/or itraconazole therapy.
Table 1: Demographics, clinical characteristics, treatment and outcome of the patients

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Figure 2: Places of residence (in Gujarat and Rajasthan province) of the patients with histoplasmosis

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Figure 3: Clinical presentation of Histoplasmosis (a) Nasolabial ulcerative lesion, (b) Palatal ulcer, (c) Computed tomography scan abdomen showing bilateral adrenal enlargement with area of necrosis within and (d) HIV infected patients with bilateral multiple pulmonary nodules

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Figure 4: Patient with multiple skin nodules over both side of face, nose and ears with vocal cord granuloma

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 ~ Discussion Top


The present study highlights 12 patients with histoplasomosis over a period of 5.5 years at two tertiary infectious disease clinics of Ahmedabad, which is considered non-endemic zone for histoplasmosis. The majority (8 of 12 patients) of those patients were apparently immunocompetent, and four patients each presented with either adrenal enlargement or oral ulcer. The timely diagnosis helped in managing 10 of 12 patients with amphotericin B deoxycholate and/or itraconazole therapy and two patients lost in follow-up.

Majority of histoplasmosis cases in India are reported in the plains of three major rivers of north and northeast India, namely, the Ganges, Yamuna and Brahmaputra. Rest part of the country is usually considered non-endemic though occasional cases were reported from those regions.[1] However, India lacks studies across the country to understand the epidemiology of histoplasmosis. The majority of the histoplasmosis cases published from this country are case reports, and few are case series from centres situated at the endemic zone.[1] Before the present series, six more cases were reported from this region in literature, five from Rajasthan and one from Gujarat.[3],[4],[5],[6],[7],[8],[9] The present report of 12 cases within relatively short period at two centres at Ahmedabad signifies that cases might be missed in the so-called non-endemic area due to lack of suspicion and laboratory facility. Histoplasma antigen detection test is not available in any laboratory of this region.

Histoplasmosis in India is largely seen in middle-aged male population with a history of soil exposure.[1] In the present study, median age of the patients was 53 years (range 34–76 years) with all male, except one. In recent review of 152 patients, the mean age of the immunocompromised patients was 37.9 ± 14.0 years (range 4–70 years) and the immunocompetent patients were 49.2 ± 14.9 years (range 3–83 years), and the male-to-female ratio was 6:1.[1] The middle-aged male preponderance in India may be explained by their outdoor agricultural activities and exposure to the fungus.

Only 4 of our 12 patients were classically immunosuppressed. The disseminated disease is common in immunosuppressed patients of India like other countries, whereas adrenal enlargement and lymphadenopathy are common in immunocompetent patients.[1] In the present report, four patients had adrenal enlargement and three had lymphadenopathy; four patients had oral ulcer. The oral ulcer due to Histoplasma was reported in immunocompetent patients of Asian countries.[10],[11] One of our patients, who had adrenal enlargement, was diagnosed as probable histoplasmosis due to raised galactomannan antigen and response to itraconazole therapy. Several workers reported the cross-reactivity of Histoplasma and Aspergillus galactomannan antigen, and it is claimed that galactomannnan antigen testing may have a role in the evaluation of patients with suspected histoplasmosis in settings where Histoplasma antigen testing is not available.[12],[13],[14],[15],[16] It would be prudent to evaluate the patients with adrenal enlargement by Aspergillus galactomannan test when sample collection is difficult technically and Histoplasma antigen test is not available.

For treatment of progressive disseminated histoplasmosis, Infectious Disease Society of America has recommended liposomal amphotericin B (3.0 mg/kg daily) for 1–2 weeks, followed by oral itraconazole (200 mg 3 times daily for 3 days and then 200 mg twice daily for a total of at least 12 months).[17] However, the majority of the patients in India are treated with amphotericin B deoxycholate and/or itraconazole. In a recent review of histoplasmosis cases, the overall mortality was reported at 14% from India; 45% of patients were treated with itraconazole alone and no death was reported in those patients.[1] In the present series, none of the patients was treated with liposomal amphotericin B due to high cost of the drug. Three of the patients received amphotericin B deoxycholate and itraconazole subsequently; five patients received only itraconazole and one patient voriconazole (due to potential drug-drug interactions with antiretroviral therapy). All those nine patients either cured or responded to therapy.

The present series highlights few important observations: Gujarat and Rajasthan provinces are also endemic for histoplasmosis and require mycology laboratory facility for diagnosis of the disease at least in all tertiary care centres; one should suspect histoplasmosis in patients with adrenal enlargement, lymphadenopathy and oral ulcer; in absence of Histoplasma antigen test Aspergillus galactomannan test may be used to support diagnosis and monitor antifungal therapy of a patient with histoplasmosis; if the patient cannot afford liposomal amphotericin B, the patient may be offered treatment with amphotericin B deoxycholate and/or itraconazole.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 ~ References Top

1.
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;182:1077-93.  Back to cited text no. 1
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2.
Deodhar D, Frenzen F, Rupali P, David D, Promila M, Ramya I, et al. Disseminated histoplasmosis: A comparative study of the clinical features and outcome among immunocompromised and immunocompetent patients. Natl Med J India 2013;26:214-5.  Back to cited text no. 2
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3.
Chejara RS, Nawal CL, Agrawal MK, Mittal P, Agrawal A, Agarwal S, et al. Progressive disseminated histoplasmosis with coomb's positive hemolytic anemia in an immunocompetent host. J Assoc Physicians India 2016;64:78-9.  Back to cited text no. 3
    
4.
Chatterjee D, Chatterjee A, Agarwal M, Mathur M, Mathur S, Mallikarjun R, et al. Disseminated histoplasmosis with oral manifestation in an immunocompetent patient. Case Rep Dent 2017;2017:1323514.  Back to cited text no. 4
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Rathod GG, Bhimani R, Aggarwal SP. Primary cutaneous histoplasmosis in 56 years old male A rare case report. Int J Curr Microbiol App Sci 2014;3:420-6.  Back to cited text no. 5
    
6.
Sareen RK, Gupta GN, Govil A. Disseminated histoplasmosis in an immunocompetent individual presenting as oropharyngeal mass. Int J Oral Health Sci 2017;7:48-52.  Back to cited text no. 6
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Gupta GV, Kothari DC. Primary histoplasmosis of oral mucosa: A rare case report. Int J Dent Med Res 2015;1:91-3.  Back to cited text no. 7
    
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Rughwani HA, Solanki B. Disseminated histoplasmosis masquerading as chronic ITP. Gujarat Med J 2015;70:98-100.  Back to cited text no. 8
    
9.
Sharma A, Nawal CL, Agarwal MK, Mital P, Chejara RS. Interesting case of disseminated histoplasmosis. J Assoc Physicians India 2016;64:116.  Back to cited text no. 9
    
10.
Padhye AA, Pathak AA, Katkar VJ, Hazare VK, Kaufman L. Oral histoplasmosis in india: A case report and an overview of cases reported during 1968-92. J Med Vet Mycol 1994;32:93-103.  Back to cited text no. 10
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Chakrabarti A, Slavin MA. Endemic fungal infections in the asia-pacific region. Med Mycol 2011;49:337-44.  Back to cited text no. 11
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Min Z, Baddley JW, Rodriguez JM, Moser SA, Patel M. Cross-reactivity of Aspergillus galactomannan in an HIV-infected patient with histoplasmosis. Med Mycol Case Rep 2012;1:119-22.  Back to cited text no. 12
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Gajurel K, Dhakal R, Deresinski S. Histoplasmosis in transplant recipients. Clin Transplant 2017;31:e13087.  Back to cited text no. 13
    
14.
Narreddy S, Chandrasekar PH. False-positive Aspergillus galactomannan (GM) assay in histoplasmosis. J Infect 2008;56:80-1.  Back to cited text no. 14
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Wheat LJ, Hackett E, Durkin M, Connolly P, Petraitiene R, Walsh TJ, et al. Histoplasmosis-associated cross-reactivity in the bioRad platelia Aspergillus enzyme immunoassay. Clin Vaccine Immunol 2007;14:638-40.  Back to cited text no. 15
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Iriart X, Blanchet D, Menard S, Lavergne RA, Chauvin P, Adenis A, et al. A complementary tool for management of disseminated Histoplasma capsulatum var. Capsulatum infections in AIDS patients. Int J Med Microbiol 2014;304:1062-5.  Back to cited text no. 16
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Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the infectious diseases society of america. Clin Infect Dis 2007;45:807-25.  Back to cited text no. 17
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