Symptomatic Schistosoma mansoni Infection as an Immune Restoration Phenomenon in a Patient Receiving Antiretroviral Therapy

Sir— We describe a case of symptomatic Schistosoma mansoni–associated enteritis presenting as an immune reconstitution inflammatory syndrome in an African man receiving antiretroviral therapy (ART). A 36-year-old South African man received the diagnosis of HIV-1 infection in 1990. He had moved to the United Kingdom in 1988 and had made no visits to Africa in subsequent years. In November 2002, his CD4+ cell count was 170 × 106 cells/L, with an HIV load of 49,700 copies/mL. ART (with tenofovir, abacavir, zidovudine, and lamivudine) was initiated. After 4 weeks, his viral load decreased to 1330 copies/mL, and his CD4+ cell count increased to 230 × 106 cells/L. Two weeks later, he developed fever, vomiting, diarrhea, and abdominal pain. Attributing these symptoms to his medication, he stopped his ART and experienced prompt symptomatic improvement. The gastrointestinal symptoms recurred 3 weeks after reinitiation of ART. During the next 2 years, his symptoms led him to stop treatment on 5 occasions; each time, the temporal association between ART and the gastrointestinal symptoms was demonstrated. The findings of microscopic evaluation of stool specimens were normal on several occasions. Colonoscopy revealed proctitis and patchy sigmoid colitis. Mucosal biopsies demonstrated numerous live and dead S. mansoni ova, with florid eosinophilic granulomatous reactions surrounding the live eggs. Schistosomal antibody ELISA results were positive. The patient was given praziquantel (40 mg/kg), and his symptoms resolved over the next 6 weeks. He remains free of gastrointestinal symptoms 2 years later. His most recent CD4+ cell count was 420 × 106 cells/L. Schistosoma eggs are highly immunogenic; granuloma formation around the ova is the characteristic histopathological appearance and is responsible for both the long-term fibrotic sequelae in the liver and the gastroenteritis seen in patients with chronic S. mansoni infection. This patient must have acquired S. mansoni infection at least 14 years previously, but he only experienced symptoms after initiation of ART. The recurrent temporal association between his symptoms and his ART regimen, together with the florid inflammatory response visualized at colonoscopy, supports the hypothesis that this is an immune restoration phenomenon [1, 2]. The inability to generate granulomas is a well-described consequence of advanced HIV infection [3]. Evidence suggests that this inability may occur in patients coinfected with S. mansoni and HIV. In animals infected with schistosomes, functional immune responses are required to generate granulomas and thus to efficiently discharge schistosome eggs across the gut mucosa [4]. A study of S. mansoni in western Kenya showed evidence of immune-facilitated excretion of schistosome eggs from patients with S. mansoni–HIV coinfection [5]. The efficiency of fecal egg excretion decreased as the peripheral CD4+ cell count decreased. A Zambian study of Schistosoma haematobium infection also showed reduced egg excretion and fewer reports of hematuria in those who were coinfected with HIV [6]. Although not all studies have replicated these findings [7, 8], this association between egg excretion and immune status supports the concept that immune reconstitution could restore antischistosomal granulomatous responses in the mucosa and lead to symptomatic enteritis, as seen in this patient. The increasing availability of ART in areas of the world where both schistosomiasis and HIV are endemic raises the possibility that Schistosoma-associated morbidity may be seen more commonly. Potential conflicts of interest. All authors: no conflicts.