8.8.7 Cystoisosporiasis 1436

8.8.7 Cystoisosporiasis 1436

section 8  Infectious diseases 1436 Prevention As with all other organisms dependent on faecal–​oral transmission, simple precautions will help prevent infection with C. cayetanensis. Water should be boiled before drinking or when used to wash fruits (although these are best peeled) or green leafy vegetables that are to be eaten raw. These measures are important in endemic areas and also when consuming fruit or vegetables that are imported from such regions, as seen with the serious outbreaks of cyclosporiasis in the United States of America due to unwashed raspberries imported from Guatemala. FURTHER READING Ashford RW (1979). Occurrence of an undescribed coccidian in man in Papua New Guinea. Ann Trop Med Parasitol, 73, 497–​500. Chacín-​Bonilla L (2010). Epidemiology of Cyclospora cayetanensis:
a review focusing in endemic areas. Acta Trop, 115, 181–​93. Eberhard ML, Pieniazak NJ, Arrowood MJ (1997). Laboratory diag- nosis of Cyclospora infections. Arch Pathol Lab Med, 121, 792–​7. Lainson R (2005). The genus Cyclospora (Apicomplexa: Eimeriidae), with a description of Cyclospora schneideri n.sp. in the snake Anilius scytale scytale (Aniliidae) from Amazonian Brazil—​a review. Mem Inst Oswaldo Cruz, 100, 103–​110. McDonald V, Kelly MP (2005). Intestinal coccidia: cryptosporidi- osis, isosporiasis, cyclosporiasis. In: Cox FEG, et al. (eds) Topley & Wilson’s microbiology & microbial infections: parasitology, 10th edition, pp. 399–​421. Hodder Arnold ASM Press, London. Ortega YR, Sanchez R (2010). Update on Cyclospora cayetanensis, a food-​borne and waterborne parasite. Clin Microbiol Rev, 23, 218–​34. Ortega YR, et  al. (1992). Cyclospora cayetanensis:  a new protozoan pathogen of humans. Abstract 289 in proceedings of the 41st annual meeting of the American Society of Tropical Medicine and Hygiene. Am J Trop Med Hyg, (Suppl), p. 210. Ortega YR, et al. (1997). Pathologic and clinical findings in patients with cyclosporiasis and a description of intracellular parasite life-​ cycle stages. J Infect Dis, 176, 1584–​9. Qvarnstrom Y, et al. (2015). Draft genome sequences from Cyclospora cayetanensis oocysts purified from a human stool sample. Genome Announcements, 3, e01324–​15. 8.8.7  Cystoisosporiasis Louis M. Weiss ESSENTIALS Cystoisospora belli is a coccidian protozoan that colonizes epithelial cells of the small intestine. Infection occurs by ingestion of para- site oocysts in water or food. Clinical features of infection include watery diarrhoea, dehydration, fever, and weight loss. Cystoisospora belli forms tissue cysts that allow for relapses of this infection. Cystoisosporiasis presenting as chronic diarrhoea is an opportunistic infection associated with HIV infection. Diagnosis is by microscopic examination of faecal specimens for C. belli oocysts, which show blue autofluorescence under ultraviolet light. Cystoisospora belli infection, even in patients with AIDS, responds rapidly to treatment with co-​trimoxazole. Introduction Cystoisospora belli causes diarrhoea in both immune competent and immune deficient patients. This diarrhoeal syndrome, however, is both more chronic and more frequently seen in patients with AIDS. Infection with this pathogen can be acquired in any country, but it is more common in tropical environments. Unlike most causes of chronic diarrhoea in the setting of AIDs, infection with this pathogen responds rapidly to drug therapy. Historical perspective While previously referred to as Isospora belli, and occasionally as I. hominis (some of these reported cases may have been due to mis- identified Sacrcocystis species), both the life cycle of this human pathogen and molecular phylogeny indicate that this organism should be a member of genus Cystoisospora, which contains over 200 species, and not Isospora. Organisms formerly included in the genus Isospora that are parasitic to mammals have now been as- signed to the genus Cystoisospora and the generic name Isospora has been retained for avian parasites. Aetiology, pathogenesis, and pathology Cystoisospora belli is a parasite of the human small intestine that causes diarrhoea. There is limited evidence that C.  belli infects non​human hosts (e.g. oocysts of C. belli have been isolated from dog faeces in India and this parasite has been transmitted experi- mentally to gibbons). Cystoisospora belli is the only member of this genus that has been clearly documented to cause human infection. There are a few reports from South Africa, in the literature prior to 1955, of a second species, C. natalensis, causing infections; however, these reports have not been subsequently confirmed. The mechan- isms responsible for the watery diarrhoea seen in infection by this pathogen are not known. The life cycle of C. belli generally occurs in a single host, with the formation of oocysts occurring 9–​17 days following infection which are passed in faeces. C. belli oocysts are ellipsoidal structures that are excreted in the faeces of infected individuals (Fig. 8.8.7.1). Studies of Cystoisospora species that parasitize non​human hosts indicate that infection occurs by ingestion of oocysts that contain sporozoites that then penetrate small intestinal epithelial cells. Evidence exists that this organism is facultatively heteroxenous (i.e. utilizes two-​hosts) and forms tissue cysts. These tissue cysts are probably the source of relapsing infections seen in immune com- promised hosts. Oocysts are generally non​infectious when passed in the faeces and complete sporulation within 1 to 5 days depending

8.8.7  Cystoisosporiasis 1437 upon the environmental conditions. Shedding of oocysts usually lasts for 30 to 50 days; however, in immune suppressed patients shedding might be prolonged, lasting over 6 months, and in such patients recrudescence of oocyst shedding occurs. This prolonged shedding is presumably due to activation of the dormant monozoic tissue cysts that can be found in a variety of tissues (e.g. lamina propria, mesenteric lymph nodes, liver, and spleen). The presence of these tissue cysts suggests that a paratenic host could be involved in the life cycle of C. belli, as has been shown to occur in Cystoisospora spp. which infect cats and dogs. Epidemiology C.  belli infection has been documented in immune competent hosts as an occasional cause of travellers’ diarrhoea and in immune suppressed individuals where it can cause a chronic diarrhoeal syndrome. In a study of 397 HIV-​infected patients in Venezuela, 56 (14%) were found to have C. belli infection (as judged by the presence of oocysts in faecal specimens). Of these 56 patients with C. belli infection, 98% had diarrhoea. C. belli infections ac- counted for 2–​3% of AIDS-​defining conditions in the 1980s, but with the widespread use of co-​trimoxazole (trimethoprim-​ sulfamethoxazole; TMP-​SMX) prophylaxis for pneumocystis pneumonia, this decreased to 0.1% by the late 1990s. Depending on the geographic region, C. belli infection was aetiologic in up to 25% of cases of chronic diarrhoea prior to the wide spread use of combination antiretroviral therapy, but has declined dramatically since its widespread use. Vehicles for transmission of C. belli oocysts to human subjects have not been identified, but presumably include water and food. Oocysts of this parasite are among the human pathogens that were found on cockroaches in a study in Nigeria, suggesting that in- sects could act as transport hosts for this pathogen. Infection with C.  belli is more commonly found in tropical, subtropical, and warm temperate region; however, indigenous infection has been reported from temperate regions. Transmission is most likely due ingestion of sporulated oocysts, and food-​ and water-​borne outbreaks have occurred. Sexual practices that permit faecal oral spread are also associated with infection. As with most faecal oral pathogens, improved sanitation and water quality decreases the risk of transmission. Clinical features In immune competent hosts a self-​limiting diarrheal illness results that lasts 2 to 3 weeks and is associated with malaise, weight loss, cramps, watery diarrhea, steatorrhea, headache, low grade fever, ab- dominal pain, vomiting, dehydration, and weight loss is seen about a week after ingestion of oocysts. In general, clinical disease is more severe in infants, young children, and in immune compromised hosts. Infection can result in a very severe illness and fatalities have occurred. Blood is not usually present in faeces. Eosinophilia is ob- served in many patients. Oocysts can be present in the faeces or bi- opsies for several months to years. Recurrences occur and have been reported as long as 10 years after initial infection. In patients infected with HIV, C.  belli infection is associated with chronic watery diarrhoea, abdominal cramps, nausea, fever, and weight loss. Severe dehydration and profound hypokalaemia can result from diarrhoea attributable to C. belli infection in HIV-​ infected patients. This can be associated with fever and weight loss. Infection has been described in patients on systemic corticosteroids being treated for eosinophilic gastroenteritis, in patients with renal or liver transplants, and in patients with haematological malignan- cies such as Hodgkin’s disease, non-​Hodgkin’s lymphoma, and adult T-​cell leukaemia. Persistent diarrhoea ascribed to isosporiasis has been described in a few HIV-​infected patients on antiretroviral therapy whose circulating CD4+ T-​cell counts were within a range that suggested immune competence. Rarely, extraintestinal C. belli infection has been described in patients with AIDS; in the relevant patients, tissues parasitized by C. belli have included gallbladder epi- thelium, liver, spleen, and mesenteric lymph nodes. In general, im- mune suppressed hosts respond to TMP-​SMX and other anti-​C. belli treatments. Laboratory diagnosis Cystisosporiasis can be diagnosed by microscopic examination of faecal specimens for C. belli oocysts. Although these structures are relatively large (20–​30 μm in length), they are translucent and can be difficult to see in unstained samples. Concentration techniques like formalin-​ethyl acetate sedimentation or sucrose centrifugal float- ation are helpful when few oocysts are present. Oocyst detection is increased by staining with carbol fuchsin, which stains oocyst in- ternal structures red, or by incubation with lactophenol cotton blue. Staining, however, can be variable and some oocysts do not stain. An alternative approach is to examine faecal smears under ultraviolet light; with this type of illumination C.  belli oocysts demonstrate blue autofluorescence. There is neither a commercial immunofluor- escence stain nor copro-​antigen assay available for the detection of this pathogen in stool. Molecular assays (e.g. polymerase chain re- action), using primers based on the small subunit RNA gene have been described and three genotypes of C. belli can be identified using restriction length polymorphisms of the small subunit RNA locus. Fig. 8.8.7.1  Light micrograph of a Cystoisospora belli oocyst (×2500). Courtesy of Dr William L. Current. From Garcia LS (2001). Diagnostic medical parasitology, 4th edition. ASM Press, Washington DC, with permission.