Indian Journal of Medical Microbiology Medknow Publications on behalf of Indian Association of Medical Microbiology ISSN: 0255-0857 EISSN: 1998-3646 Vol. 29, Num. 2, 2011, pp. 188-191

Indian Journal of Medical Microbiology, Vol. 29, No. 2, April-June, 2011, pp. 188-191

Case Report

A rare case of Histoplasma fungemia in an AIDS patient

VP Baradkar, U Tendolkar, S Baveja, S Kamath

Department of Microbiology, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai - 400 020, India

Correspondence Address:V P Baradkar Department of Microbiology, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai - 400 020 India vasantbaradkar@yahoo.com

Date of Submission: 14-Aug-2010
Date of Acceptance: 30-Jan-2011

Code Number: mb11045

PMID: 21654120

DOI: 10.4103/0255-0857.81792

Abstract

Keywords: Acquired immune deficiency syndrome, blood culture, Histoplasma capsulatum, histoplasmosis

Introduction

Histoplasmosis is not an uncommonly reported disease in India. In India, numerous cases have been reported since the first case report in 1954. ^[1] Most of these cases were diagnosed by histopathological examination. ^[2] but only few cases were confirmed by culture. From 1968 to 1992, 25 authentic histoplasmosis cases have been reported from India. In 19 out of these 25 cases, the lesions were confined only to the oral cavity. ^[3] Thus disseminated cases of histoplasmosis are rarely reported from India. Among the co-morbid conditions associated with 19 cases of disseminated histoplasmosis reported by Subramanian et al.,^[4] diabetes mellitus and HIV were the most common conditions. Most of the case reports mention the isolation of the fungus from various sites like bone marrow, lymph node aspirate, spleenic aspirate and biopsies. ^{[1],[2],[3],[4]} Progressive disseminated histoplasmosis occurs mostly in immunocompromised patients or at extremes of age. Organisms can be seen in fungal staining of biopsies from pulmonary and other tissues. They are less commonly seen in peripheral blood smears. ^{[1],[2],[3],[4]} On scanning the literature from India we did not come across any published report of isolation of Histoplasma from blood culture. We report a case of disseminated histoplasmosis in an AIDS patient and recovery of the fungus from blood culture.

Case Report

A 30-year-old, married, unemployed male from Uttar Pradesh was admitted to a private hospital with intermittent low to moderate fever since two months, loss of appetite and nausea. He also had cough with mucoid expectoration. The patient was HIV seropositive and the cause of his acute febrile illness was provisionally diagnosed as malaria. Tuberculosis was also suspected due to the presenting symptoms. The patient was treated in the private hospital for malaria. He was diagnosed as HIV seropositive by ELISA and Western Blot which were performed in the private hospital. His fever did not subside. The patient was then admitted in our hospital. On examination he was febrile. His general condition was moderate. Pulse rate was 80/min and blood pressure was 120/80 mm of Hg. Pallor, mild cyanosis, and mild conjunctival congestion was present. On auscultation a few crepitations were observed at the bases of both the lungs. Findings of the cardiovascular system were within normal limits. Per-abdominal examination showed that there was generalized tenderness present with a palpable liver. Spleen was not palpable and there was no free fluid in the abdomen. After admission to our hospital the patient was treated with injectable artisunate (120 mg OD), metronidazole (100 cc TDS), amikacin (100 mg BD), and ampicillin (500 mg OD). Doxycycline was given orally (100 mg BD). His haematological investigations showed that haemoglobin was 9.5 gm%. Total leucocyte count was 1500 cell/mm ³ with polymorphs 74%, lymphocytes 23% and monocytes 3%. His platelet count was 124000 cell/mm ³ . Erythocyte sedimentation rate (E) was 170 mm/h and Red blood count (RBC) count was 2.42 million/mm ³ . Findings of Liver function tests and Kidney function tests showed that blood urea creatine (BUN) was 25 mg%, serum creatine was 1.1 mg% and serum bilirubin was 0.8%. His bone marrow examination was done on the fifth day of admission due to persistent underlying fever, which showed hypocellular bone marrow with depletion cells of erythropioitic and megakerotocyte series. Yeast forms, intracellular and a few extracellular were observed [Figure - 1]. A fungal aetiology, Histoplasma capsulatum was suspected. On the 11 ^th day of admission, blood samples were collected in a sterile heparinised syringe and transported in a sterile tube. Blood was then centrifuged and the deposit was observed on Gram′s stain and Giemsa stain. The deposit was cultured on two sets of Sabouraud′s dextrose agar (SDA) and brain heart infusion blood agar (BHIBA). Giemsa staining showed few intracellular 2-4μ narrow-necked budding yeast cells inside neutrophils. Gram′s staining also showed Gram-positive budding yeast cells. One SDA was incubated at 37 ⁰ C and another at room temperature. After about three weeks whitish velvety colonies were observed on SDA. The isolate was confirmed as Histoplasma capsulatum by routine mycological procedures ^[5] [Figure - 2]. Conversion to yeast form could be demonstrated on repeated subcultures on BHIBA moistened with addition of 2 ml of brain heart infusion broth [Figure - 3]. Meanwhile the patient was started with amphotericin B on the 11 ^th day, but his condition deteriorated and he died.

Discussion

Histoplasmosis has been reported both in immunocompetent as well as immunocompromised patients, with the disseminated form being common in the latter group. ^[1] Unlike in the United States, no clearly demarcated foci have been identified in India. However a large number of cases have been reported from eastern India. ^[2] Studies on skin sensitivity to histoplasmin which were carried out between 1952 to 1972 have shown a sensitivity ranging from 0-12.3% in eastern India. ^[2] Interest in histoplasmosis in India peaked in the 1970s when as many as 20 cases of the disease had been reported from the eastern part of the country. ^[6] In an extensive review spanning 25 years (1968-1992) and encompassing 29 cases, Padhye et al., ^[3] have shown that out of 25 cases successfully diagnosed, the fungus was cultured in only 13 cases. In the year 2005, Subramanian et al., ^[4] retrospectively analysed 19 cases of disseminated histoplasmosis during a 10-year period (1989-1999).

Acute progressive disseminated histoplasmosis (PDH) was earlier uncommon, but is now frequently reported from AIDS cases in endemic areas. There are only few cases of acute PDH reported in AIDS patients in India including the report of Subramanian et al,^[4] Singhi et al,^[7] reported it from the north-eastern region while Mohanchand et al.,^[8] in the year 2000 reported a case of PDH in an AIDS patient from Mumbai. The patient was a 28-year-old sailor, unmarried and he originally belonged to Assam. In both these cases the diagnosis of acute PDH was done only on histopathological grounds and fungal cultures were negative. Recently, in the year 2006, Joshi et al.,^[9] from Pune (Maharashtra) reported a case of acute PDH in a 45-year-old AIDS patient who was a manual labourer working at a construction site. They diagnosed histoplasmosis based on bone marrow and spleen aspirate. Mc Kinsy et al.,^[10] have shown that Histoplasma capsulatum can be demonstrated in peripheral blood smear in about 28% of cases.

Our case report is unique in the sense that Histoplasma capsulatum was demonstrated on peripheral blood smear and it was also isolated from blood. Blood collection in a syringe with citrate solution and centrifugation is a known technique for blood culture of Leishmania donovani. The same technique for blood culture was adopted for the present case since both the organisms circulate in blood and lodge in bone marrow. Centrifugation of blood has the added advantage of concentrating the organisms in blood. ^[11] A blood culture and smear for fungi prior to performing bone marrow aspiration, which is an invasive procedure, would have been more beneficial to the patient. Oropharyngeal ulcers, erythematous papules, and nodules which may be found in disseminated histoplasmosis were absent in our patient.

Laboratory investigations from previous studies showed presence of anaemia, raised erythrocyte sedimentation rate (ESR), and thrombocytopenia which were present in our case. Renal and hepatic function tests also were altered. ¹⁴ Amphotericin B is the drug of choice for the treatment of disseminated histoplasmosis. Our patient was started with amphotericin B, in spite of which he succumbed to death. Awareness of this infection and early treatment is important because 100% mortality seen in the untreated group comes down to 70% when adequately treated with amphotericin B. ^[1],[2]

It can be deduced from the findings of this case that histoplasmosis should be suspected in all cases of fever of unknown origin, especially in HIV-positive subjects. For the diagnosis of this potentially life-threatening condition, a simple blood examination prior to any painful invasive procedures like bone marrow aspiration, biopsies etc. may help in an early diagnosis with institution of appropriate therapy.

Acknowledgment

We acknowledge Dr. N. B. Agarwal, consultant haematologist, Mumbai for his support and for giving the bone marrow smear of the patient.

References

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