Cyclospora and cyclosporiasis

Article about cyclospora and cyclosporiasis.

Cyclospora cayetanensis under microscope stained

Topics covered: 

  • Essentials
  • Introduction
  • Life cycle
  • Epidemiology
  • Clinical features
  • Diagnosis
  • Pathology
  • Treatment
  • Prevention
  • Further reading

Essentials

Most species of Cyclospora (Protozoa: Apicomplexa: Eimeriidae) are parasites of various reptiles and mammals. C. cayetanensis, which probably infects only humans, is transmitted by way of resistant oocysts voided in the faeces and contaminating food or water. Distribution is worldwide, particularly in regions with a low level of hygiene. Clinical presentation is with explosive outbreaks of acute diarrhoea, with this infection now regarded as an important causative agent of traveller’s diarrhoea. Diagnosis is dependent on detection of oocysts in faeces by direct examination or in stained faecal smears. Aside from supportive care, treatment with trimethoprim–sulfamethoxazole has proved effective in eliminating the parasite in immunocompetent patients, but relapses are common in those with AIDS. Prevention is by ensuring good general hygiene, and in areas of high endemicity water should be boiled before drinking or use in preparation of fruits/vegetables that are to be eaten raw.

Introduction

Species of the coccidian genus Cyclospora (Protozoa: Apicomplexa: Eimeriidae) have been recorded in invertebrates (millipedes), reptiles (principally snakes), insectivores (moles), rodents, and primates (monkeys and humans). Endogenous development of most species is within the epithelial cells of the small intestine, culminating in the production of oocysts, which are voided in the faeces and serve as the means of transmission. Small, bisporocystic coccidial oocysts detected in the faeces of patients with diarrhoea in Papua New Guinea almost certainly represented the first discovery of cyclospora in humans in 1979, but due to difficulties in determining the number of sporozoites in each sporocyst, the parasite was not identified to generic level. What were clearly unsporulated oocysts of the same parasite, seen by other authors in patients with diarrhoea, were for many years referred to as ‘cryptosporidium-like oocysts’, ‘cyanobacterium-like bodies’ (bodies resembling blue-green algae), or even ‘fungal spores’, and it was not until 1992 that the exact nature of the cysts was established and the parasite named as Cyclospora cayetanensis.

Life cycle 

Cyclospora species have been most extensively studied in nonhuman hosts, in which stages of development are typically intracytoplasmic in the epithelial cells of the small intestine. An exception is C. talpae of the mole Talpa europaea, which develops within the nucleus of the epithelial cells of the bile ducts and cells of the capillary sinusoids in the liver. Asexual reproduction (merogony) is followed by the production of female gametocytes (macrogamonts) and male gametocytes (microgamonts) that produce a large number of flagellated gametes.

Cyclospora cayetanensis, a Food-Borne and Waterborne Parasite

Above: Cyclospora cayetanensis, a Food-Borne and Waterborne Parasite

Following fertilization of the female parasites, the zygotes develop a resistant membrane. The resulting oocysts are voided, unsporulated, in the host’s faeces.

During periods varying from a few days to 1 or 2 weeks, depending on the species of Cyclospora and the temperature of the contaminated environment, the zygote within the oocyst undergoes division to produce two sporoblasts , each of which develops a resistant membrane, the sporocyst. Division of each sporoblast then gives rise to two elongate sporozoites, leaving a conspicuous residual body. The sporozoites are the stages that infect further animals of the same species when oocysts are ingested with contaminated food or water.

Life cycle of Cyclospora cayetanensis

Above: Life cycle of Cyclospora cayetanensis

Epidemiology 

Failure to experimentally infect a variety of animals or to detect C. cayetanensis in those living in or near houses with human infection has led to the conclusion that humans are the specific host of this coccidian and the sole source of its oocysts. The parasite is globally distributed, although risk of infection is greatest in developing countries with low standards of hygiene. It is particularly prevalent in Central America and southern Asia. Serious outbreaks of acute diarrhoea have been reported, however, among guests at social events in the United States of America and Canada, with the source of infection traced to imported raspberries from Guatemala. Another outbreak, in Germany, occurred among a group of 34 people who had eaten a salad of imported lettuce spiced with fresh leafy herbs. In other countries, oocysts of C. cayetanensis have been detected on green leafy vegetables, in sewage, and even in tap water. Clinical features Top Previous Next An acute, watery, and nonbloody diarrhoea is variously accompanied by abdominal pain, steatorrhoea, headache, fever, nausea, and general malaise. The diarrhoea may be persistent and last for several weeks. Asymptomatic infections are known to occur, notably in the indigenous population of developing countries.

US Map of states reporting Cyclospora infections as of August 1, 2013

Above: US Map of states reporting Cyclospora infections as of August 1, 2013

Diagnosis 

Diagnosis is dependent on the demonstration of oocysts of C. cayetanensis in the faeces by direct microscopic examination. Flotation methods, using saturated sugar or aqueous zinc sulphate solutions, are useful in concentrating the oocysts, which measure from 8.0 to 10.0 μm in diameter (average 8.6 μm).

Oocyst of Cyclospora cayetanensis in unstained wet mounts of stool. Image taken at 1000x magnification

Above: Oocyst of Cyclospora cayetanensis in unstained wet mounts of stool. Image taken at 1000x magnification

The living oocysts are autofluorescent using ultraviolet illumination, which is useful for rapid diagnosis. In addition, most diagnostic laboratories use a variety of staining methods to colour the oocysts in faecal smears fixed in 10% formalin: notably, modified Ziehl–Neelsen acid-fast staining, and safranin stain. These do not reveal details of the oocyst contents, but their size and spherical shape readily distinguishes them from other coccidian oocysts or sporocysts that may be stained by the same methods. The polymerase chain reaction with primers specific for C. cayetanensis also affords a highly sensitive, but more costly, diagnostic technique. 

There are four other intestinal coccidia that infect humans and may produce similar symptoms, but they are morphologically readily differentiated from C. cayetanensis when viewed unstained. The oocysts of cryptosporidium, also an important cause of acute diarrhoea, are spherical but are only from 4.5 to 5.0 μm in diameter (half the size of C. cayetanensis oocysts) and they contain four naked sporozoites. Isospora belli oocysts are elongated, measure from 25 to 33 μm in length and from 12 to 16 μm in width, and have two sporocysts, each of which contains four sporozoites. Humans are the definite host of two species of Sarcocystis, S. hominis and S. suihominis: unlike C. cayetanensis, their oocysts undergo endogenous sporulation and contain two sporocysts, each containing four sporozoites. The oocysts are very fragile and usually rupture, so that only free sporocysts may be found in the faeces. These are easily differentiated from C. cayetanensis oocysts by their larger size (average 16 μm × 10.5 μm) and ellipsoidal shape. 

A well-trained microscopist will have no difficulty in distinguishing other protozoa of the human intestine. Among these are the cystic stages of Entamoeba histolytica and Giardia lamblia and the non-cystic Dientamoeba fragilis, all of which commonly cause abdominal pain and diarrhoea. 

Pathology 

Histology of jejunal biopsies from patients with cyclosporiasis has shown blunting and widening of infected villi and an intense lymphocytic infiltration in the lamina propria and overlying epithelium. There is a diffuse oedema, together with reactive hyperaemia and vascular dilation that is accompanied by congestion of the villous capillaries.

Treatment 

Co-trimoxazole (960 mg two times daily for 1 week) has proved effective in eliminating the parasite in immunocompetent patients and has been shown successfully to control relapses in those with AIDS by the administration of 960 mg three times a week, indefinitely. Ciprofloxacin (500 mg two times daily for 1 week) is recommended for patients who react badly to sulphonamides.

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 not only important in the endemic areas of developing countries, but need to be taken 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. 

wash vegetables to prevent food poisoning - e.g. cyclospora

Above: Prevention - wash vegetables to prevent food poisoning - e.g. cyclospora

Further reading

Top

Ashford RW (1979). Occurrence of an undescribed coccidian in man in Papua New Guinea. Ann Trop Med Parasitol, 73, 497–500. [Web of Science] [Medline]

Eberhard ML, Pieniazak NJ, Arrowood MJ (1997). Laboratory diagnosis of Cyclospora infections. Arch Pathol Lab Med, 121, 792–7. [Web of Science] [Medline]

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. [Web of Science] [Medline]

McDonald V, Kelly MP (2005). Intestinal coccidia: cryptosporidiosis, 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, 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, Gilman RH, Sterling CR (1994). A new coccidian parasite (Apicomplexa: Eimeriidae) from humans. J Parasitol, 80, 625–9.[CrossRef] [Medline]

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.