Clinical Brief
Refractory Isosporiasis Sonia Malik, J.C. Samantaray, Arvind Bagga I and Anupam Das
Departments of Microbiology and ~Pediatrics,All India Institute of Medical Sciences, New Delhi, India
Abstract. The authors describe a case of severe debilitating diarrhea due to isosporiasis in a two year old child, a known case of systemic vasculitis receiving prolonged corticosteroids therapy, an association rarely reported previously. It was refractory to treatment with dihydrofolate reductase inhibitor combined with sulfonamide such as cotrimoxazole to which isosporiasis usually responds well and is being described here for clinical interest and uniqu?ness of its presentation and laboratory findings. [Indian J Pediatr 2005; 72 (5) : 437-439] E-mail:
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Key words : Isosporiasis; Steroids; Recurrence Isosporiasis is a diarrheal illness caused in humans by Isospora belliand is cosmopolitan in distribution; although more common in southeast Asia, Africa, and parts of South America. 1It produces self limiting watery diarrhea in i m m u n o c o m p e t e n t hosts and chronic severe debilitating watery diarrhea in immunocompromised patients. 2 Opportunistic isosporidial infection of the gastrointestinal tract is frequently encountered in AIDS patients and is considered an AIDS defining illness. 3 Besides AIDS, chronic severe watery diarrhea due to Isospora belli has also been reported in other immunodeficiency states. 1 We describe here severe debilitating diarrhea due to isosporiasis in a patient receiving prolonged corticosteroids therapy, an association rarely reported previously, which was refractory to treatment with dihydrofolate reductase inhibitor combined with sulfonamide such as cotrimoxazole to which isosporiasis usually responds well. CASE REPORT
The patient, a two year child, who was on tapering steroid therapy (receiving 7.5 m g / d a y prednisolone at that time) since eight months and oral cyclophosphamide (2-3 mg/kg/day), was admitted to pediatrics ward with history of sudden onset severe watery diarrhea of one week duration. The child was a known case of systemic vasculitis. The stools were watery in consistency with a frequency of 15-20 episodes per day. He also had associated low grade fever with productive cough for the last one week as well as oral thrush. The child was grossly malnourished ( PEM grade III). Laboratory examination showed Hb 13.1gm%, TLC 5300/mm 3(N 64%, L-28%,
Correspondence and Reprint requests : Dr. I.C. Samantaray, Professor,Deptt.of Microbiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India. Fax: 91-01126588641/8663. Indian Journal of Pediatrics, Volume 72--May, 2005
E-8%), SGOT 51U/L, SGPT 56U/L, Alkaline phosphatase 96U/L, Blood urea 14 mg/dl, Serum creatinine 0.5 mg/dl, total bilirubin 0.7 mg/dl, Uric acid 2.2mg/dl. Serology was negative for antinuclear and antineutrophilic cytoplasmic antibodies. His immunoglobulin profile was within normal range. The patient's serum was negative for anti-HIV antibodies by ELISA and his CD4 and CD8 counts were 330/gl and 544/gl respectively. His stool sample was sent to rule out any parasitological etiology. The stool was watery in consistency with visible shreds of mucous membrane. A direct wet saline and an iodine mount were prepared from the stool sample with an effort to include part of mucous shred in the sampling. Direct wet mount examination revealed large numbers of epithelial cells, pus cells (30-40/HPF, mainly eosinophils), numerous Charcoat-Leyden crystals(10-15/HPF) and red blood cells (5-10/HPF). Oocysts of Isospora belli, (predominantly immature) intermingled within the mucous membrane were seen in an overwhelmingly high number (approximately 20-25/HPF). They were long and oval, measuring 20-31 g x11-19 g on micrometry. Also seen on wet mount (400X) were some banana shaped curved structures (5-7/HPF) with one end more rounded than the other and measuring 10-13 x 4-5 g in size. On the basis of characteristic morphology and size 4, these structures were identified to be merozoites of Isospora (Fig. 1). Modified Ziehl-Neelsen staining technique 5 revealed Isospora oocysts (Fig. 2) many of which were partially stained and some unstained. Bacterial culture of the stool performed as per standard protocols 6 did not grow any pathogenic bacteria. Stool was not examined for any pathogenic viruses. The child was treated with oral cotrimoxazole (Trimethoprim 20 m g / k g / d a y and sulphamethoxazole 100 m g / k g / d a y ) for 10 days. The diarrhoea ceased within three days and the patient's subsequent stool sample after a period of seven days did not reveal any Isospora oocyst. The child gained weight and was 437
Sonia Malik et al
Fig. 1. Isosporabellioocyst(bigblackarrow) and Isosporamerozoite (small black arrow) seen in wet saline mount (400x). Inset: Isosporamerozoitemagnified(640x) (Scale: 10p; inset 5~1)
Fig. 2. ModifiedZiehl-Neelsen staining showing Isospora belli oocysts,some partiallystained and some unstained (100x). Inset : Isosporaoocystmagnified(1000x). discharged after eight days of stay in hospital. Three weeks later, the child again developed an episode of acute diarrhoea, which was also confirmed to be due to Isospora, and it responded to cotrimoxazole with stool becoming negative for Isospora oocysts. He later developed four recurrences of isosporiasis and was prescribed prolonged cotrimoxazole prophylactic therapy. However, cotrimoxazole had to be discontinued due to drug reaction and the parents of the child abandoned the treatment and switched to alternate system of medicine (ayurvedic therapy). The child continued to have diarrheal episodes and eventually died of severe malnutrition and hepatic failure ( severe jaundice) as revealed by parents later. DISCUSSION
Isosporiasis has been commonly reported in immunocompromised patients with AIDS. It has also been observed in patients with Hodgkin's disease, non 438
Hodgkin's lymphoproliferative disease or acute lymphoblastic leukaemia. 1Only once previously has it been described in association with steroid use. Morakote et al reported a case of acute isosporiasis from Thailand in a patient with underlying Nephrotic syndrome, who had received prednisolone 60mg/day for 13 days.7 The patient recovered from diarrhoea without any specific treatment. There are several remarkable features in the present case, which make it unique. This patient not only had severe diarrhoea due to Isospora, he had recurrent episodes of isosporiasis, a phenomenon usually observed in severely immunodeficient AIDS patients with CD4 counts
