Endogenous development of Cystoisospora belli in intestinal and biliary epithelium of humans

Abstract

Cystoisospora (Isospora) belli is a coccidian parasite of humans. It can cause serious digestive disorders involving infection of intestines, biliary tract and gallbladder, especially in those with depressed immunity. It has a direct fecal–oral transmission cycle. After ingestion of sporulated oocysts, the parasite multiplies asexually and sexually within host epithelial cells, resulting in unsporulated oocysts that are excreted in feces. The details of asexual and sexual stages are not known and certain inclusions in epithelial cells in biopsy samples have been erroneously identified recently as C. belli. Here, we provide details of developmental stages of C. belli in two patients, in duodenal biopsy of one and biliary epithelium of the other. Immature and mature asexual stages (schizonts/meronts) were seen in epithelial cells. The merozoites were seen singly, in pairs and in groups in single parasitophorous vacuole (pv) in host cytoplasm. Immature and mature meronts were seen together in the same pv; up to eight nuclei were seen in meronts that retained elongated crescent shape; round multinucleated schizonts, seen in other coccidians, were not found. Meronts were up to 25 µm long and contained up to ten merozoites that were 8–11 µm long. The merozoites and meronts contained PAS-positive granules. Microgamonts (male) contained up to 30 nuclei that were arranged at the periphery and had condensed chromatin; 1–3 PAS-positive, eosinophilic, residual bodies were left when microgametes were formed. The microgametes were 4 µm long and PAS-negative. All stages of macrogamonts, including oocysts were PAS-positive. The detailed description of the life cycle stages of C. belli reported here should facilitate in histopathologic diagnosis of this parasite.

Cystoisospora belliinfections in humans: the past 100 years

“…Therefore, an intensive search was made to identify the developmental stages of C. belli in the duodenum and common bile duct of two patients reported previously (Walther and Topazian, 2009; Swanson et al ., 2018). The study revealed that C. belli schizonts and gamonts were like other species of Cystoisospora in animals (Dubey et al ., 2019). Schizonts were often crescent-shaped, up to 25 × 18 µ m, and contained up to 10 merozoites that were 10–11 × 3–4 µ m. The macrogamonts were elongated.…”

“…The microgamonts contained as many as 30 nuclei, and 1–3 residual bodies. The microgametes are about 4 µ m long (Dubey et al ., 2019) and have flagella. The life cycle of C. belli is illustrated in Fig.…”

Life Cycle and Transmission of Cyclospora cayetanensis: Knowns and Unknowns

“…Cystoisospora belli is another coccidian that also parasitizes the small intestine and biliary system in humans [14,15]. In Cystoisospora, different generations of schizonts/Types can be found in the same host cell, because schizonts can rupture inside the host cell and merozoites can multiply within the same host cell without exiting the host cell (Figure 3).…”

“…Whether this type of multiplication also occurs in C. cayetanensis remains to be determined. Because C. belli stages (including merozoites, gamonts and oocysts) are more than twice the size of their counterparts in C. cayetanensis, differential diagnosis is possible to the trained eye using light microscopy [15]. Genetic assays also support differential diagnosis [16][17][18].…”

Pitfalls in Morphologic Diagnosis of Pathogens: Lessons Learned From the Pseudo-Cystoisospora Epidemic

“…Involvement of the gallbladder and biliary tract rarely occurs. 1-7 Within the last 5 years, multiple groups have reported parasite infestation of the gallbladder in immunocompetent patients, especially in acalculous cholecystitis. 8-17 This led to an increased screening of gallbladder specimens for the organism by the pathologist and antibiotic treatment in some of the diagnosed patients.…”