Pneumonia and pleural effusion due to Cryptococcus laurentii in a clinically proven case of AIDS

1Mycoplasma Laboratory of the Department of Microbiology, Dr ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus; 2YR Gaitonde Centre for AIDS Research and Education, Voluntary Health Services Campus, Taramani, Chennai, Tamilnadu, India Correspondence: Dr Usha Anand Rao, Mycoplasma Laboratory of the Department of Microbiology, Dr ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600113, Tamilnadu, India. Telephone 91-22-24925317, fax 91-44-24927609, e-mail drushaanand@yahoo.com EM Shankar, N Kumarasamy, D Bella, et al. Pneumonia and pleural effusion due to Cryptococcus laurentii in a clinically proven case of AIDS. Can Respir J 2006;13(5):275-278.

Pneumonia and pleural effusion due to Cryptococcus laurentii in a clinically proven case of AIDS C ryptococcosis, usually due to Cryptococcus neoformans, is considered to be one of the most serious fungal infections in immunocompromised patients.In the past, non-neoformans species have been generally regarded as nonpathogenic saprophytes.However, in recent years, opportunistic infections associated with Cryptococcus albidus, Cryptococcus curvatus, Cryptococcus humicolus, Cryptococcus uniguttulatus and Cryptococcus laurentii have been reported (1)(2)(3)(4)(5)(6).
C laurentii, a basidiomycetous encapsulated yeast, is present in the droppings and cloacal samples of feral pigeons (7).C laurentii is used as a biopesticide and is efficient in controlling fruit rot in apples (8,9).C laurentii has recently been reported as a cause of pulmonary and cutaneous infections in humans.Interestingly, there are only 16 reported cases of disease caused by C laurentii infection.We report a case of pulmonary cryptococcosis resulting from C laurentii, along with Moraxella catarrhalis and Klebsiella pneumoniae infections, in a diabetic patient with AIDS, in whom complete clinical resolution occurred after oral fluconazole administration.

CASE PRESENTATION
A 35-year-old diabetic woman with clinically proven AIDS was admitted in September 2005 to the inpatient department of the YR Gaitonde Centre for AIDS Research and Education, a specialized AIDS care and research institution in Chennai, India.The patient presented with a febrile illness, breathlessness, dysphagia, odynophagia, vomiting, headache, cough and sputum, night sweats, malaise and left pleuritic chest pain for approximately one week.She was diagnosed with HIV infection in 2001 consequent to bouts of fever, diarrhea, aphthosis, rectal and genital ulcers, and weight loss.The patient complained of producing thick, mucopurulent sputum for the past few months and had been on some form of antiretroviral therapy with zidovudine for the past four years.At the time of admission, she was also on Pneumocystis carinii pneumonia prophylaxis with trimethoprim-sulfamethoxazole (160 mg/day trimethoprim and 800 mg/day sulfamethoxazole) and antituberculosis treatment with two months of daily isoniazid, rifampicin, ethambutol and pyrazinamide, followed by a sevenmonth continuation phase of daily isoniazid and rifampicin.On examination, the patient had a temperature of 38.5°C, a pulse of 106 beats/min, a blood pressure of 110/70 mmHg and blood oxygen saturation of 96%.She was thin, conscious, oriented and edema-free.A chest examination revealed reduced expansion on the left, quiet breath sounds, dullness to percussion in the left infrascapular region and tan-coloured, thick, mucopurulent sputum.She also presented with rales and coarse crepitations on auscultation.An abdominal examination revealed hepatosplenomegaly.A chest x-ray revealed extensive left pleural effusion (Figure 1).Laboratory examinations revealed that she had a random blood glucose of 9.8 mmol/L (normal values 4.4 mmol/L to 6.6 mmol/L), hemoglobin of 73 g/L (normal values 120 g/L to 150 g/L), total leukocyte count of 6.9×10 9 /L (normal values 4×10 9 /L to 11×10 9 /L), total lymphocyte count of 0.2×10 9 /L (normal values 0.8×10 9 /L to 3.2×10 9 /L), erythrocyte sedimentation rate of greater than 125 mm/h (normal values 0 mm/h to 30 mm/h) and a total platelet count of 161×10 9  Pleural fluid drained on day 2 (200 mL) did not reveal any bacterial growth.A sputum examination showed Gram-negative, large, round to oval yeast cells (Figure 2A) that were initially misinterpreted as non-albicans Candida.Gram-negative intracellular diplococci and capsulated bacilli were also observed in the sputum, and were identified as M catarrhalis and K pneumoniae, respectively.The sputum and pleural fluid were negative for acid-fast bacilli (AFB) by Ziehl-Neelsen staining.The patient felt better after the pleural drainage and underwent blood transfusion on days 3 and 4. On day 5, she developed fever with a severe cough and dyspnea.Sputum smears were negative for AFB.Sputum and pleural fluid cultures on Sabouraud's dextrose agar with chloramphenicol (without cycloheximide) at 48 h revealed a few 1 mm to 2 mm in diameter, smooth, cream-coloured, poorly grown mucoid colonies and 2 mm to 3 mm in diameter mucoid colonies at 37°C and 25°C, respectively.No yeast cells were observed on pleural smear examination.Nigrosin staining revealed encapsulated, elongated, budding yeast cells with thickened cell walls and capsules; these cells were identified as C laurentii (Figure 2).The yeast was repeatedly encountered in pleural fluid culture.Antifungal therapy with oral fluconazole 600 mg/day for five weeks was started, along with oral ceftrioxone 1 g/day to 2 g/day for clearance of bacteria.Culture of both respiratory samples (BACTEC TB culture system, BD Biosciences, USA) did not reveal AFB.The patient responded well to the treatment and was discharged.

DISCUSSION
Cryptococci generally occur in soil contaminated with pigeon feces (10) and are transmitted to humans primarily through inhaled fomites.Species other than C neoformans have generally been thought to be nonpathogenic to humans (4,11,12).Although C laurentii has been reported as occurring worldwide, its natural habitat has not yet been thoroughly established.Cryptococcosis, an uncommon disease before the AIDS epidemic, has emerged as an important cause of illness and death in HIV-infected patients.However, there are little data on the isolation of C laurentii from the respiratory tract of AIDS patients; to date, only 16 cases, including the present report, have been published (these reports are summarized in Table 1).Thus, the present report is significant in that it potentially describes the first case of pneumonia resulting from C laurentii in the Indian HIV population.
Most patients with cryptococcosis suffer from substantial T cell dysfunction, as do patients with AIDS (13).Other immunological defects associated with cryptococcosis are lymphopenia and immune dysfunctions (14).Our patient was severely lymphopenic, as evidenced by laboratory results (total lymphotcyte count of 0.2×10 9 /L).The repeated isolation of C laurentii from pleural fluid and sputum indicated that it was probably the cause of the pneumonic disease in our patient, although the pleural fluid did not reveal the yeast on direct examination.The involvement of AFB in the pleural fluid was also ruled out by negative AFB culture.The pleural fluid was bacteriologically sterile, ruling out other bacterial infections of the pleural space; M catarrhalis and K pneumoniae were isolated only from the sputum, not from the pleural fluid.The patient had initially felt better after pleural drainage, which could be the result of a possible reduction of the yeast  population in the fluid.There was no laboratory evidence of P carinii, possibly because the patient was on trimethoprimsulfamethoxazole prophylaxis.
There is no validated standard treatment for C laurentii infection.Correlations between in vitro antifungal susceptibility test results and treatment outcomes do not exist for C laurentii.However, the patient tolerated oral fluconazole well and, with pleural drainage, the outcome was favourable.Feral pigeons may be carriers of C laurentii (7), but details on the patient's previous contact with pigeons were unavailable.She did, however, live in close proximity to agricultural areas and pastures.Because isolation of C laurentii from plants and soil has been previously reported ), a rural habitat and possible exposure to yeast, combined with underlying predisposing conditions, may have made our patient vulnerable to infection.Extensive surveillance of the patient's living environment could provide more insight into her acquisition of the yeast.A review of the literature showed only two reports pertaining to infection involving the respiratory tract: one involving a lung abscess (12) and the other involving pneumonia (16).Our patient is the second to be diagnosed with an AIDS and C laurentii coinfection; the first was a patient with meningitis (3).

CONCLUSIONS
The present report is the first to describe the rare pulmonary involvement of C laurentii in the Indian HIV population.The pulmonary symptoms may be noncharacteristic, but a high degree of suspicion and improvement of culture and identification techniques will contribute to the early diagnosis, treatment and management of unusual fungal infections in HIV/AIDS patients.

Figure 1 )Figure 2 )
Figure 1) Chest x-ray showing extensive left pleural effusion Cryptococcus laurentii in AIDS Can Respir J Vol 13 No 5 July/August 2006 277

TABLE 1
Summary of data from cases of Cryptococcus laurentii infection in humans