Indian Pediatrics 2001; 38: 667-670
Trichosporonosis in a Previously Healthy Child in Nepal
From the Departments of Pediatrics and Microbio-logy*,
B.P. Koirala Institute of Health Sciences, Dharan, Nepal.
Manuscript received: June 27, 2000; Initial review completed: August 3, 2000; Revision accepted: January 1, 2001.
Trichosporon beigelii is a fungus related to Cryptococcus belonging to same phylum, Basidiomycota and sharing partial molecular sequences. In humans, this fungus commonly causes hair-infection resulting in white piedra. Invasive disease called Trichosporonosis due to T. Beigelii is rare and is believed to occur almost exclusively in the immuno-compromised. In the present report we describe a case of systemic Trichosporonosis in a previously healthy child hailing from the hills of Eastern Nepal.
An 11-year-old boy, resident of a hilly area of Eastern Nepal presented to Pediatric ward of BPKIHS with complaints of progressive breathlessness for three weeks, distention of abdomen and swelling over scrotum and lower limbs for 10 days. There was no history of fever, trauma, rashes, vomiting or jaundice. The child belonged to a low socio-economic class farmer family. His appetite was reduced during this illness. He did not give a history of any habit disorder. His growth and developmental history was normal and he was attending local school. There was no family history of tuberculosis, diabetes or similar illness.
On physical examination, the patient was a young boy of average built having body weight of 24 kg. He had mild respiratory distress with fullness and decreased movements on right side of the chest. Trachea was shifted to left. Air entry was reduced on right side and there was stony dullness on percussion. Liver was enlarged 8 cm below costal margin. Shifting dullness was present in abdomen with bilateral scrotal swelling. He had no jaundice, cyanosis, clubbing but had bilateral pedal edema. A provisional diagnosis of right sided pleural effusion likely to be tubercular was considered.
His investigations revealed Hb, TLC and DLC of 12.4 g/dl, 4300 cu mm, P42 L58, respectively. His ESR was 19 mm in 1st hour and Mantoux test was negative. Plain X-ray chest revealed findings of right sided pleural effusion. The findings of pleural tap were: color-turbid, WBC 190/cu mm, N5 L95, protein 5 g/dl, and sugar 76 mg/dl. The fluid was bacteriologically sterile. Staining revealed fungal hyphae with characteristic arthroconidia. The fungus was isolated on three separate occasions from pleural fluid. It was identified as T. beigelii on the basis of presence of arthroconidia on Gramís stain, colony morphology on Sabouraudís dextrose agar and urease production. Pleural fluid was also examined for Mycobacteria by direct smear examination and culture and was negative for acid-fast organisms by both the methods. Gastric aspirate obtained on three consecutive days was also negative for Mycobacteria by smear examination and culture. His liver function tests showed total bilirubin, ALT and alkaline phosphatase to be 1.64 mg/dl, 36 U/L and 336 U/L, respectively. His HIV testing was negative and rest of biochemical investigations were within normal limits.
The child was managed conservatively on oral ketoconazole followed by Amphotericin B. During the course of his admission he also developed pleural effusion of left side which improved on continuing the therapy. Keto-conazole was administered in the dose of 10 mg/kg/day for 10 days. Amphotericin B was given in increasing dosages for 5 days. The child showed marked improvement with reduction in size of liver and disappearance of pleural effusion. Following clinical and complete radiological improvement, the child was discharged on 24th day with the advice to continue Ketoconazole for a further period of 7 days as it could be given orally. Parents were asked to bring the child for follow-up but they didnít turn up.
The first case of systemic Trichosporon infection was reported in 1970(1) in a 39 year old woman with a metastatic lung cancer involving the brain. Post-mortem. T. beigelii was isolated in culture from brain lesions. Predisposing risk factors for invasive T. beigelii infection are neutropenia, heart-valve surgery, treatment with corticosteroids, intra-venous catheters, extensive burn and AIDS(2). Cases have been reported in immuno-compromised children and newborns(3).
The source of human Trichosporon is believed to be patientís own endogenous mycobiota. Mucosal colonization, which may be enhanced by empirical antibiotic therapy and subsequent seeding of the blood stream through breaks in the integrity of the surface are believed to be the early steps in the pathophysiology of invasive disease. Direct seeding of the site of infections has also been reported including wound infections(4). Trichosporonosis is most frequently reported in neutropenic patients implying neutrophils as the most important defense mechanism against this fungus(5). Isolates of T. beigelii are more resistant to phagocytosis by neutrophils and monocytes than Candida albicans and effective killing occurs only if the poly-morphonuclear leukocytes outnumber the fungus(6). No virulence factors have been reported except a cell wall antigen similar to glucuronoxylomannan of Cryptococcus neoformans(5).
Clinically, invasive trichosporonosis may occur in disseminated or localized forms, former being more common. Formation of hyphae may assist in the invasion of tissues(7). An acute febrile illness not responding to antibacterial therapy, rapidly progressing to multi-organ failure and sepsis syndrome characterize invasive trichosporo-nosis; lungs and kidneys are most commonly involved. Localized invasive infection confined to heart valves, CNS, peritoneum and surgical wounds have also been described.
The source of T. beigelii in our patient could not be ascertained. It is unlikely to be from the hospital environment since the fungus was not isolated from any other patient in the pediatrics ward during the prolonged stay of our patient. Possibly, the source is endogenous, but no predisposing risk factors for invasive disease by this fungus was detectable. Failure to find any bacteriological cause, including Mycobacteria, lack of clinical response to empirical antibacterials, isolation of T. beigelii from a normally sterile site (pleural fluid), and good response to antifungal therapy point to an etiological role by this rare fungus.
Response to treatment with antifungals is frequently poor in patients with invasive T. beigelli infection, due to profound immuno-suppression and serious underlying conditions presenting a therapeutic challenge(2). Conser-vative management with single antifungal agent like Amphotericin B, flucytosine, fluconazole and ketoconazole has been effective in only few cases. Resistance to Amphotericin B and evolution of disease, often fatal progression despite continuing amphotericin B has been described(8). While successful treatment with liposomal ampho-tericin B(3) and itraconazole(9) has been reported, most of the workers suggest a combination antifungal therapy. Removal of catheters along with antifungals has also been helpful in certain situations. In some cases splenectomy was beneficial.
The clinical experience worldwide has shown that the drug used for the treatment of trichosporonosis is probably not as important as the status of the underlying disease of the host(2) and immunological recovery is the most important factor for favorable out-come(10). The rapid clinical improvement seen in our patient following administration of antifungals could possibly be attributed to intact immune function. This case illustrates the need for clinical vigilance in situations unresponsive to conventional anti-infective therapy and seek laboratory evidence for rare mycotic agents to institute appropriate management strategies.
Contributors: KS was responsible for work-up, literature review and drafting the manuscript. He will act as the guarantor for the paper. VGR was responsible for microbiological isolation, literature review, final review and draft of the manuscript. VK was responsible for day to day care of the child and manuscript preparation. BK did microbiological processing and analysis. RS was responsible for overall management and manuscript review.