Abstract
Cystoisospora belli causes chronic diarrhoea, acalculous cholecystitis, cholangiopathy and disseminated cystoisosporosis in patients with AIDS. Clinical manifestations and histological stages during C. belli infection in a patient with AIDS and liver disease were described. It was possible to identify sporozoite-like structures in the villus epithelium of the duodenum, close to the vascularization that underlies the basal membrane and unizoite tissue cysts near to the vascularization in the lamina propria. Unizoite tissue cysts were found inside of sinusoids in the liver communicating with the central vein and with a bile canaliculus and portal spaces. Based on these findings a hypothesis on C. belli life cycle could consider that the route of migration of unizoite tissue cysts up the liver is via the portal blood. The unizoite tissue cysts located in hepatic portal vein could migrated via sinusoid to central vein and general circulation through the venous system. The unizoite tissue cysts could also return via bile canaliculus to bile duct to portal triad. This hypothesis allows to understand the presence of unizoite stages in blood, the pathway by which the bile ducts become infected and unizoites in the liver being able to behave like hypnozoites that favour relapses and treatment failures.
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References
Benator DA, French AL, Beaudet LM, Levy CS, Orenstein JM 1994 Isospora belli infection associated with acalculous cholecystitis in a patient with AIDS. Ann Intern Med 121:663-664. doi: 10.7326/0003-4819-121-9-199411010-00006
Comin CE, Santucci M (1994) Submicroscopic profile of Isospora belli enteritis in a patient with acquired immune deficiency syndrome. Ultrastruct Pathol 18:473–482. https://doi.org/10.3109/01913129409023222
Dhingra S, Ward SC, Thung SN (2016) Liver pathology of hepatitis C, beyond grading and staging of the disease. World J Gastroenterol 22:1357–1366. https://doi.org/10.3748/wjg.v22.i4.1357
Dubey JP (1975) Experimental Isospora canis and Isospora felis infection in mice, cats, and dogs. J Protozool 22:416–417. https://doi.org/10.1111/j.1550-7408.1975.tb05195.x
Dubey JP (2014) Life cycle of Cystoisospora felis (Coccidia: Apicomplexa) in cats and mice. J Eukaryot Microbiol 61:637–643. https://doi.org/10.1111/jeu.12145
Dubey JP (2018) A review of Cystoisospora felis and C. rivolta-induced coccidiosis in cats. Vet Parasitol 263:34–48. https://doi.org/10.1016/j.vetpar.2018.09.016
Dubey JP, Almeria S 2019 Cystoisospora belli infections in humans: the past 100 years. Parasitology 146:1490-1527. doi: https://doi.org/10.1017/S0031182019000957.
Dubey JP, Evason KJ, Walther Z (2019) Endogenous development of Cystoisospora belli in intestinal and biliary epithelium of humans. Parasitology 146:865–872. https://doi.org/10.1017/S003118201900012X
Dubey JP, Frenkel JK (1972) Extra-intestinal stages of Isospora felis and I. rivolta (Protozoa: Eimeriidae) in cats. J Protozool 19:89–92. https://doi.org/10.1111/j.1550-7408.1972.tb03419.x
Frenkel JK, Silva MB, Saldanha JC, de Silva-Vergara ML, Correia D, Barata CH, Silva EL, Ramirez LE, Prata A (2003) Presença extra-intestinal de cistos unizóicos de Isospora belli em paciente com SIDA: relato de caso [Extraintestinal finding of Isospora belli unizoic cysts in a patient with AIDS: case report]. Rev Soc Bras Med Trop 36:409–412. https://doi.org/10.1590/s0037-86822003000300014
Horton R (1967) The route of migration of Eimeria stiedae (Lindemann, 1865) sporozoites between the duodenum and bile ducts of the rabbit. Parasitology 57:9–17. https://doi.org/10.1017/S0031182000071857
Koudela B, Modrý D (1999) Extraintestinal stages of coccidia in liver of Schneider's skink Eumeces schneideri (Sauria: Scincidae) from northern Egypt. Folia Parasitologica 46:99–102
Lindsay DS, Dubey JP, Blagburn BL (1997) Biology of Isospora spp. from humans, nonhuman primates, and domestic animals. Clin Microbiol Rev 10:19–34. https://doi.org/10.1128/CMR.10.1.19-34.1997
Markus MB (1991) Origin of extra-intestinal stages of Isospora belli in the acquired immune deficiency syndrome (AIDS). Med Hypotheses 35:278. https://doi.org/10.1016/0306-9877(91)90246-u
Michiels JF, Hofman P, Bernard E, Saint Paul MC, Boissy C, Mondain V, LeFichoux Y, Loubiere R (1994) Intestinal and extraintestinal Isospora belli infection in an AIDS patient. A second case report. Pathol Res Pract 190:1089–1094. https://doi.org/10.1016/S0344-0338(11)80908-8
Montalvo R, Ticona E, Ñavincopa M, García Y, Chávez G, Chávez V, Arévalo J, Soria J, Huiza A (2013) Diarrea recurrente por Cystoisopora belli en pacientes con infección por VIH con TARGA [Recurrent diarrhea due to Cystoisopora belli in HIV/AIDS patients receiving HAART]. Rev Peru Med Exp Salud Publica 30:326–330. https://doi.org/10.17843/RPMESP.2013.302.213
Pakandl M (2009) Coccidia of rabbit: a review. Folia Parasitol (Praha) 56:153–166. https://doi.org/10.14411/fp.2009.019
Restrepo C, Macher AM, Radany EH (1987) Disseminated extraintestinal isosporiasis in a patient with acquired immune deficiency syndrome. Am J Clin Pathol 87:536–542. https://doi.org/10.1093/ajcp/87.4.536
Samarasinghe B, Johnson J, Ryan U (2008) Phylogenetic analysis of Cystoisospora species at the rRNA ITS1 locus and development of a PCR-RFLP assay. Exp Parasitol 118:592–595. https://doi.org/10.1016/j.exppara.2007.10.015
Silva-Díaz H, Fernández-Valverde D, Hernández-Córdova G, Failoc-Rojas VE (2017) Infección por Cystoisospora belli en pacientes con VIH: análisis de casos con diferente evolución clínica [Cystoisospora belli infection in HIV patients: analysis of cases with different clinical evolution]. Rev Chilena Infectol 34:347–351. https://doi.org/10.4067/s0716-10182017000400347
Smetana H (1933) Coccidiosis of the liver of rabbits: experimental study of the mode of infection of the liver by sporozoites. Archs Path 15:330–339
Soresi M, Carroccio A, Bonfissuto G, Agate V, Magliarisi C, Aragona F, Levrero M, Notarbartolo A, Montalto G (1998) Ultrasound detection of abdominal lymphadenomegaly in subjects with hepatitis C virus infection and persistently normal transaminases: a predictive index of liver histology severity. J Hepatol 28:544–549. https://doi.org/10.1016/s0168-8278(98)80276-6
Velásquez JN, Carnevale S, Mariano M, Kuo LH, Caballero A, Chertcoff A, Ibáñez C, Bozzini JP (2001) Isosporosis and unizoite tissue cysts in patients with acquired immunodeficiency syndrome. Hum Pathol 32:500–505. https://doi.org/10.1053/hupa.2001.24326
Velásquez JN, di Risio CA, Etchart CB, Chertcoff AV, Nigro MG, Pantano ML, Ledesma BA, Vittar N, Carnevale S (2016) First report of Cystoisospora belli parasitemia in a patient with acquired immunodeficiency syndrome. Acta Parasitol 61:172–177. https://doi.org/10.1515/ap-2016-0023
Velásquez JN, Osvaldo GA, Di Risio C, Etchart C, Chertcoff AV, Perissé GE, Carnevale S (2011) Molecular characterization of Cystoisospora belli and unizoite tissue cyst in patients with Acquired Immunodeficiency Syndrome. Parasitology 138:279–286. https://doi.org/10.1017/S0031182010001253
Walther Z, Topazian MD 2009 Isospora cholangiopathy: case study with histologic characterization and molecular confirmation. Hum Pathol 40:1342-1346. doi: 10.1016/j.humpath.2009.01.020
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The Ethical Committee for Research of the Hospital Francisco J. Muñiz, approved this research protocol registered under the number 274. Written informed consent from the patient was obtained.
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Velásquez, J.N., Etchart, C.B., Astudillo, O.G. et al. Cystoisospora belli, liver disease and hypothesis on the life cycle. Parasitol Res 121, 403–411 (2022). https://doi.org/10.1007/s00436-021-07406-2
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DOI: https://doi.org/10.1007/s00436-021-07406-2