Original Article
Cyclospora Species -- A New Protozoan Pathogen of Humans
N Engl J Med 1993; 328:1308-1312May 6, 1993
- Abstract
Background
Organisms referred to as “cyanobacterium-like bodies” have now been identified worldwide in the feces of both immunocompetent and immunocompromised patients with diarrhea. Organisms with a similar appearance have been isolated from Peruvian patients since 1985. From 1988 to 1991 we studied prospectively two cohorts of infants and young children infected with this organism. We now attempt to identify it.
Methods
Fecal samples were collected weekly from the children and examined with the use of acid-fast staining and staining with a monoclonal antibody specific for cryptosporidium. Stools positive for cyanobacterium-like bodies were preserved in potassium dichromate and exposed to conditions allowing coccidian sporulation and excystation. Both unsporulated and sporulated oocysts were fixed by freeze-substitution techniques and then examined by electron microscopy.
Results
Organisms isolated from the feces of Peruvian patients and two patients from the United States were identified as belonging to the coccidian genus cyclospora, after sporulation and excystation of the oocysts according to standard techniques. Complete sporulation occurred within 5 to 13 days in oocysts maintained in potassium dichromate at 25 or 32 °C. Complete excystation resulted in the liberation of two sporozoites from the two sporocysts within each oocyst (cryptosporidia have four naked sporozoites within each oocyst). The presence of organelles characteristic of coccidian organisms was confirmed by electron microscopy.
Conclusions
We have identified organisms of the genus cyclospora that are remarkably similar to cryptosporidia in their morphologic features and the diarrheal disease that they produce in humans. The complete life cycle and epidemiology of this new protozoan parasite remain to be described.
Media in This Article
Figure 1
Oocysts of a Cyclospora Species (Panel A), Cryptosporidium muris (Panel B), and C. parvum (Panel C) (Modified Acid-Fast Stain).Figure 2
Sporulation and Excystation.Article Activity
- Article
Spherical organisms that are 8 to 10 micrometers in diameter and have variable characteristics on acid-fast staining are being identified with increasing frequency in feces from both immunocompetent visitors to developing countries and immunocompromised patients with chronic diarrhea in the United States1-8. The first reported cases of infection with such organisms attributed the illness to an unsporulated, coccidian body or a fungal spore1. The patients were immunologically competent, had traveled from the United States to either Mexico or Haiti, and reported a “flu-like” illness accompanied by nausea, vomiting, anorexia, weight loss, and explosive watery diarrhea lasting one to three weeks. Subsequent reports of infection caused by these organisms described cyst forms isolated from feces that suggested the presence of a new pathogen that might be a Cryptosporidium muris-like oocyst,2 a flagellate,2 an unsporulated coccidian,4 a large cryptosporidium,5 a blue-green alga (cyanobacterium-like body),5-8 or a coccidian-like body5,7,8. In almost every instance, the symptoms were attributed solely to the presence of the organism, either because other enteropathogens could not be isolated or because the patients did not respond to normally effective antimicrobial treatments.
In the largest study of immunocompetent patients, illness was associated with a prolonged but self-limiting diarrhea (lasting a mean [±SD] of 43 ±24 days)8. A pattern of relapsing diarrhea lasting up to four weeks was noted among several physicians at a Chicago hospital who were excreting this organism,6 and epidemiologic investigation indicated that they had been exposed to a contaminated water source. The association of this organism with prolonged illness in patients with the acquired immunodeficiency syndrome (AIDS) is less clear, since few patients with both AIDS and the organism have been studied to date5. In one study a patient died within two weeks after the organism had been detected,4 and in another study intestinal symptoms were reported to clear within two weeks5.
The organisms have been observed in fecal smears after the application of either phenosafranin or modified acid-fast stains, although both are highly variable in their ability to stain the cyst5,7. In addition, the organisms have been reported to show autofluorescence when examined by ultraviolet epifluorescence7. On light microscopy they are nonrefractile spheres 8 to 10 micrometers in diameter containing a cluster of refractile, membrane-bound globules enclosed within a membrane (morula). A single division of the morula occurred after the organism was cultured in distilled water for 7 days, but no further development followed prolonged cultivation (>7 months)7. Preliminary electron-microscopical examination revealed a spherical object with an outer fibrillar coat and a thick cell wall. The internal cytoplasm, which contained light and dark granules, was bound by cell membrane. In addition, the presence of lamellar structures, suggestive of thylakoid membranes from chloroplasts, and the absence of a nucleus suggested that the organism might be prokaryotic, resembling cyanobacteria5.
This report describes the positive identification of the organism and provides evidence of a new protozoan pathogen that infects humans.
Methods
Sample Collection and Identification of Isolates
Collaborative efforts between investigators of the University of Arizona, the Johns Hopkins University, and Universidad Peruana Cayetano Heredia began in 1985 with the express purpose of defining the epidemiology of C. parvum infections in children living in the slums of Lima, Peru. The initial work focused on the transfer of technological means that would permit easier, more specific identification of cryptosporidium oocysts from the feces of infected children and adults with the use of fluorescence-labeled monoclonal antibodies9. During these studies, fecal samples were also evaluated with a modified acid-fast stain to corroborate the findings of the investigation with oocyst-specific monoclonal antibodies.
From January 1988 to October 1991, two large-scale, prospective cohort studies were conducted in the shantytowns of Lima. The first study was initiated to define the epidemiology of C. parvum in children, and the second to determine the role of breast milk in protecting urban Peruvian children against this infection10. Together, these studies involved weekly examination of feces from 377 children ranging in age from one month to more than two years. Stool samples were examined after both modified acid-fast staining and immunofluorescence reaction with a monoclonal antibody (Merifluor, Meridian Diagnostics, Cincinnati).
Sporulation
Organisms resembling cyanobacterium-like bodies, isolated from the subjects with the heaviest infections in the second study, were preserved in 2.5 percent potassium dichromate for further study. Because the organisms in freshly collected feces bore a strong resemblance to unsporulated coccidian oocysts, sporulation was attempted at different temperatures. Feces preserved in potassium dichromate that were less than two weeks old were layered over a primary discontinuous sucrose gradient (densities, 1.064 and 1.103 g per liter) and centrifuged (1500 × g for 25 minutes)11. Organisms purified by this procedure were then placed in 2.5 percent potassium dichromate in covered petri dishes and incubated in room air at 4, 25, 32, or 37 °C12. Daily changes in the appearance of the organism were monitored by phase-contrast microscopy.
Excystation
Organisms from cultures kept at 25 or 32 °C were mechanically ruptured to liberate sporocysts and then subjected to procedures for coccidian excystation with 0.5 percent trypsin and 1.5 percent sodium taurocholate in phosphate-buffered saline11.
Transmission Electron Microscopy
Unsporulated organisms and organisms that had undergone sporulation for five days at 25 °C also were fixed for electron microscopy according to freeze-substitution techniques13.
Results
Organism Identification and Patient History
In 1985, spherical cyst-like organisms measuring 8 to 10 micrometers in diameter were observed in the feces of a 65-year-old Peruvian woman presenting with severe chronic diarrhea2. The organisms, shown in Figure 1Figure 1
Oocysts of a Cyclospora Species (Panel A), Cryptosporidium muris (Panel B), and C. parvum (Panel C) (Modified Acid-Fast Stain)., had a variably mottled, red appearance on modified acid-fast staining and resembled the oocysts of C. muris; for comparison, oocysts of C. muris from an infected beef cow are shown in Figure 1B, and those of C. parvum from an infected Peruvian child in Figure 1C.In 1987, two additional patients presented with somewhat similar symptoms and acid-fast organisms in their feces. The first of these was a 33-year-old American missionary studying the Quechua language in the jungles of Peru, who had come to Lima for treatment of diarrhea. He presented in early April with a watery diarrhea, which continued intermittently for more than three weeks. At endoscopy 3 1/2 weeks after presentation, biopsy samples were taken from the antrum and body of the stomach and from the duodenum. The biopsy sites were selected in the hope of finding developing parasites that might resemble C. muris, which develops at these sites in both mice and cows. At the time of biopsy, the organism was no longer detectable in the patient's feces, and the biopsy showed nothing unusual.
During the same period a 50-year-old Peruvian woman who was a wholesale meat vendor presented with watery diarrhea and the same acid-fast organisms in her feces. For at least one month she had a pattern of three to five watery bowel movements per day for three or four days, followed by normal bowel movements for two days. Endoscopy was performed as in the other patient, while she was still shedding organisms; the findings were unremarkable. She continued to shed organisms intermittently in her feces for an additional two weeks but had no symptoms. After this time, organisms were no longer detectable in her feces. Informed consent for biopsies was obtained from both patients after the nature and possible consequences of the study had been fully explained to them.
Epidemiologic Investigation
At presentation, 18 percent of the children in the first study (26 subjects) and 6 percent of those in the second (15 subjects) had C. muris-like cysts in their feces. These cysts were easily distinguished from the oocysts of C. parvum (which are 4 to 6 micrometers in diameter) because they were larger and because they did not react with a monoclonal antibody with 100 percent sensitivity and specificity for C. parvum oocysts14. As in other studies, the reaction of the organisms with the modified acid-fast stain was highly variable: some organisms stained dark red and had a variable number of dark inclusion bodies, whereas others did not stain at all and appeared as transparent spheres. In addition, the organisms showed a fairly strong green autofluorescence when observed under ultraviolet epifluorescence. Six children in the first study and three in the second study each had two episodes of infection with the C. muris-like organism. Of the children subsequently found to be infected with cyclospora species, 28 percent of those in the first study (nine subjects) and 11 percent of those in the second study (two subjects) presented with diarrhea. The mean duration of shedding of organisms was remarkably similar in both studies (22.4 days [range, 7 to 70] vs. 23.3 days [range, 7 to 50]). Since the age at enrollment in the two studies differed, this variable could not be compared. The differences in the features of infection between the new organism and C. parvum are shown in Table 1Table 1
Comparison of Features of Infection with C. parvum and a Cyclospora Species in Two Prospective Cohort Studies of Peruvian Children.. Infections with this new organism also showed seasonal tendencies, with peaks between April and June.Sporulation
Sporulation of approximately 20 percent of the organisms, which resulted in the formation of two sporocysts similar in appearance to those previously reported,7 was noticed by day 5 in cultures kept at 25 or 32 °C (Figure 2AFigure 2
Sporulation and Excystation.). Complete sporulation, resulting in the appearance of sporozoites within sporocysts, became evident between days 7 and 13 in cultures. Feces that had been kept at 4 °C in potassium dichromate for four to six months contained organisms that appeared to have already undergone sporulation. Organisms maintained at 37 °C showed a contraction and darkening of the central cell mass after five days in culture.Excystation
Within 15 minutes of exposure to the excysting solution at 37 °C, movement was observed in each sporocyst; within 30 minutes, two crescent-shaped sporozoites measuring 1.2 by 9.0 micrometers emerged from one of the sporocysts (Figure 2B). Complete excystation, with the liberation of four sporozoites, was observed within 40 minutes of exposure to the excysting solution (Figure 2C and Figure 2D).
Microscopical Findings
The features of both unsporulated (Figure 3AFigure 3
Features of a Cyclospora Species on Transmission Electron Microscopy.) and sporulated (Figure 3B) organisms observed on electron microscopy indicated that the organisms were coccidian. The immature oocyst had an outer fibrillar coat of 63 nm, beneath which lay a cell wall 50 nm thick. The internal cytoplasmic mass contained light and dark granules similar to those previously found in cyanobacterium-like bodies. The mature oocyst had a fibrillar coat and cell wall similar to that of the unsporulated oocyst. Each sporocyst had a wall 62 nm thick. The sporozoites within the sporocyst had a membrane-bound nucleus and micronemes characteristic of coccidians of the phylum Apicomplexa (Figure 3B).Discussion
The observations made during sporulation and excystation and the characteristic features of the new organism are sufficient evidence to place it within the coccidian genus cyclospora. Organisms belonging to this genus have an oocyst with two sporocysts, each with two sporozoites15. This description, therefore, is very much like that of isosporan parasites of humans except that isosporans are usually larger and have an oocyst with two sporocysts, each with four sporozoites15. Our finding also provides evidence that the organisms recently described as cyanobacterium-like bodies in patients in North, Central, and South America, Caribbean countries, Southeast Asia, and Eastern Europe may in fact be a new coccidian pathogen of the genus cyclospora. This conclusion is also supported by the descriptions in these reports of the organism's characteristics on evaluation with modified acid-fast stains, its autofluorescence under ultraviolet epifluorescence, and its replication in culture; the clinical features of infection; and the resistance of the infection to conventional antimicrobial therapy. More important, organisms similar to cyanobacterium-like bodies that were isolated from the feces of two patients with diarrhea in Los Angeles and Chicago in May and July 1992, respectively, and sent to us for further studies also have been confirmed as cyclospora. Our initial report, which speculated that this organism was a flagellate,2 is obviously incorrect. In all likelihood the organisms referred to in that abstract2 were immature cysts of Giardia intestinalis, another common parasite of children in the shantytowns of Peru.
What is now apparent from the published reports about the cyanobacterium-like bodies and the C. muris-like organism is that persons of all ages can become infected, although rates of diarrhea may prove to be lower among those from zones where these pathogens are endemic. This will have to be confirmed by conducting epidemiologic studies in those areas. The fact that infection with cyclospora occurs at the same time of year as does infection with cryptosporidium in Peru implies that the acquisition of infection may be associated with similar risk factors.
Organisms of the genus cyclospora have previously been found only in reptiles,16 myriapods,17 insectivores,18-23 and one murine host24. The oocysts reported in those animals, however, are sufficiently different in size from those reported in humans to warrant regarding the human parasite as a new species. The complete life cycle and epidemiologic features of this new parasite remain unknown. The difference in sporulation time that we noted during the present study (7 to 13 days) may merely reflect the age of the sample when sporulation was initiated.
Except for prolonged intermittent diarrhea, the clinical presentation of patients infected with this organism was quite similar to the presentation of those infected with C. parvum. Because the new organism is acid-fast like the oocyst of cryptosporidium, we strongly recommend that all laboratories screening for the latter parasite provide precise measurements of oocysts. In developing countries, where size discriminations are often not made, it is quite possible that many cases of diarrhea reported to be due to cryptosporidium might actually have been due to cyclospora. Because the cyclospora organism also has been seen in patients with AIDS and intractable diarrhea, this infection should be carefully distinguished from cryptosporidiosis. There is obviously a great deal more to learn about this emerging pathogen.
Supported in part by Thrasher Research Funds (2798-5 and 2803-7).
We are indebted to the personnel of Asociacion Benefica PRISMA and the entire staff of the parasitology laboratory at Universidad Peruana Cayetano Heredia for their support; to Dr. Jorge Naranjo and Dr. Elba Miranda for their contributions; to Dr. John Gilkey for his outstanding technical assistance with the freeze-substitution electron miscroscopy; and to Lynn Garcia, Dr. Frank Kocka, and Dr. Becky Wurtz for the samples from the patients in Los Angeles and Chicago.
Source Information
From the Department of Veterinary Science, University of Arizona, Tucson (Y.R.O., C.R.S., V.A.C.); the Department of International Health, Johns Hopkins University, Baltimore (R.H.G.); and the Departamento de Parasitologia, Universidad Peruana Cayetano Heredia, and the Asociacion Benefica PRISMA, both in Lima, Peru (R.H.G., F.D.).
Address reprint requests to Dr. Sterling at the Department of Veterinary Science, University of Arizona, Bldg. 90, Rm. 201, Tucson, AZ 85721.
- References
References
1
Soave R ,Dubey JP ,Ramos LJ ,Tummings M . A new intestinal pathogen? Clin Res 1986;34:533A-533A abstract.2
Naranjo J, Sterling CR, Gilman R. Cryptosporidium muris-like objects from fecal samples of Peruvians. Presented at the 38th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Honolulu, December 10-14, 1989. abstract.
3
Taylor DN ,Houston R ,Shlim DR ,Bhaibulaya M ,Ungar BLP ,Echevarria P . Etiology of diarrhea among travelers and foreign residents in Nepal. JAMA 1988;260:1245-1248
CrossRef | Web of Science | Medline4
Hart AS ,Ridinger MT ,Soundarajan R ,Peters CS ,Swiatlo AL ,Kocka FE . Novel organisms associated with chronic diarrhoea in AIDS. Lancet 1990;335:169-170
CrossRef | Web of Science | Medline5
Long EG ,Ebrahimzadeh A ,White EH ,Swisher B ,Callaway CS . Alga associated with diarrhea in patients with acquired immunodeficiency syndrome and in travelers. J Clin Microbiol 1990;28:1101-1104
Web of Science | Medline6
Outbreaks of diarrheal illness associated with cyanobacteria (blue-green algae)-like bodies -- Chicago and Nepal, 1989 and 1990MMWR Morb Mortal Wkly Rep 1991;40:325-327
Medline7
Long EG ,White EH ,Carmichael WW , et al. Morphologic and staining characteristics of a cyanobacterium-like organism associated with diarrhea. J Infect Dis 1991;164:199-202
CrossRef | Web of Science | Medline8
Shlim DR ,Cohen MT ,Eaton M ,Rajah R ,Long EG ,Ungar BL . An alga-like organism associated with an outbreak of prolonged diarrhea among foreigners in Nepal. Am J Trop Med Hyg 1991;45:383-389
Web of Science | Medline9
Sterling CR ,Arrowood MJ . Detection of Cryptosporidium sp. infections using a direct immunofluorescent assay. Pediatr Infect Dis 1986;5:Suppl:S139-S142
CrossRef | Medline10
Sterling CR ,Gilman RH ,Sinclair NA ,Cama V ,Castillo R ,Diaz F . The role of breast milk in protecting urban Peruvian children against Cryptosporidiosis. J Protozool 1991;38:Suppl:23S-25S
Medline11
Arrowood MJ ,Sterling CR . Isolation of Cryptosporidium oocysts and sporozoites using discontinuous sucrose and isopycnic Percoll gradients. J Parasitol 1987;73:314-319
CrossRef | Web of Science | Medline12
Dubey JP ,Miller NL ,Frenkel JK . The Toxoplasma gondii oocyst from cat feces. J Exp Med 1970;132:636-662
CrossRef | Web of Science | Medline13
Bridgman PC ,Reese TS . The structure of cytoplasm in directly frozen cultured cells. I. Filamentous meshworks and the cytoplasmic ground substance. J Cell Biol 1984;99:1655-1668
CrossRef | Web of Science | Medline14
Garcia LS ,Brewer TC ,Bruckner DA . Fluorescence detection of Cryptosporidium oocysts in human fecal specimens by using monoclonal antibodies. J Clin Microbiol 1987;25:119-121
Medline15
Levine ND. Introduction, history, and taxonomy. In: Hammond DM, Long PL, eds. The coccidia: eimeria, isospora, toxoplasma, and related genera. Baltimore: University Park Press, 1973:1-22.
16
Pellerdy L. Coccidia and coccidiosis. 2nd ed. Berlin, Germany: Paul Parey, 1974:959.
17
Schneider A . Sur les psorospermies oviformes ou coccidies: especes nouvelles ou peu connues. Arch Zool Exp 1881;1:387-40418
Schaudinn F . Studien uber krankheitserregende Protozoen I. Cyclospora caryolytica Schaud., der Erreger der perniciosen Enteritis des Maulwurfs. Arbeit Kaiserl Gesundh 1901;18:378-41619
Pellerdy L ,Tanyi J . Cyclospora talpae sp. n. (Protozoa: sporozoa) from the liver of Talpa europaea. Folia Parasitol (Praha) 1968;15:275-27720
Duszynski DW ,Wattam AR . Coccidian parasites (Apicomplexa: Eimeriidae) from insectivores. IV. Four new species in Talpa europaea from England. J Protozool 1988;35:58-62
Medline21
Ford PL ,Duszynski DW . Coccidian parasites (Apicomplexa: Eimeriidea) from insectivores. VI. Six new species from the eastern mole, Scalopus aquaticus. J Protozool 1988;35:223-226
Medline22
Ford PL ,Duszynski DW . Coccidian parasites (Apicomplexa: Eimeriidea) from insectivores. VII. Six new species from the hairy-tailed mole, Parascalops breweri. J Parasitol 1989;75:508-513
CrossRef | Web of Science | Medline23
Mohamed HA ,Molyneux DH . Developmental stages of Cyclospora talpae in the liver and bile duct of the mole (Talpa europaea). Parasitology 1990;101:345-350
CrossRef | Web of Science | Medline24
Ford PL ,Duszynski DW ,McAllister CT . Coccidia (Apicomplexa) from heteromyid rodents in the southwestern United States, Baja California, and northern Mexico with three new species from Chaetodipus hispidus. J Parasitol 1990;76:325-331
CrossRef | Web of Science | Medline
- Citing Articles (81)
Citing Articles
1
F. MILORD, E. LAMPRON-GOULET, M. ST-AMOUR, E. LEVAC, D. RAMSAY. (2011) Cyclospora cayetanensis: a description of clinical aspects of an outbreak in Quebec, Canada. Epidemiology and Infection1-7
CrossRef2
T.N. Petney, H. Taraschewski. 2011. Waterborne Parasitic Diseases: Hydrology, Regional Development, and Control. , 303-366.
CrossRef3
Leonor Chacín-Bonilla. (2010) Epidemiology of Cyclospora cayetanensis: A review focusing in endemic areas. Acta Tropica 115:3, 181-193
CrossRef4
Vincent McDonald, M. Paul Kelly. 2010. Intestinal Coccidia: Cryptosporidiosis, Isosporiasis, Cyclosporiasis. .
CrossRef5
Nancy J. Cox, Gabriele Neumann, Ruben O. Donis, Yoshihiro Kawaoka. 2010. Orthomyxoviruses: Influenza. .
CrossRef6
F.E.G. Cox. 2010. History of Human Parasitology. .
CrossRef7
Gabriel A. Schmunis, Francisco J. López-Antuñano. 2010. World-Wide Importance of Parasites. .
CrossRef8
M. Eugenia Portillo, Alejandra Pérez-García, Mirian Fernández-Alonso, Manuel Rubio. (2010) Diarrea del viajero por Cyclospora cayetanensis. Medicina Clínica 134:8, 377-378
CrossRef9
H. Smith, R. Evans. 2009. Parasites: Cryptosporidium, Giardia, Cyclospora, Entamoeba histolytica, Toxoplasma gondii and pathogenic free-living amoebae ( Acanthamoeba spp. and Naegleria fowleri) as foodborne pathogens. , 930-1008.
CrossRef10
Nguyen Thuy Tram, Linda M. N. Hoang, Phung Dac Cam, Phan Thu Chung, Murray W. Fyfe, Judith L. Isaac-Renton, Corinne S. L. Ong. (2008) Cyclospora spp. in herbs and water samples collected from markets and farms in Hanoi, Vietnam. Tropical Medicine & International Health 13:11, 1415-1420
CrossRef11
Carmen C. Mundaca, Paola A. Torres-Slimming, Roger V. Araujo-Castillo, Manuel Morán, David J. Bacon, Ynes Ortega, Robert H. Gilman, David L. Blazes. (2008) Use of PCR to improve diagnostic yield in an outbreak of cyclosporiasis in Lima, Peru. Transactions of the Royal Society of Tropical Medicine and Hygiene 102:7, 712-717
CrossRef12
Francis Derouin, Marie Lagrange-Xelot. (2008) Treatment of parasitic diarrhea in HIV-infected patients. Expert Review of Anti-infective Therapy 6:3, 337-349
CrossRef13
Barbara M. Lund. 2008. Properties of Microorganisms that Cause Foodborne Disease. , 12-233.
CrossRef14
Kammili Nagamani, Pavuluri Pandu Ranga Rao, Gyaneshwari Mathur, Gudiseva Thandava Phani Krishna, Anuradha Pattepu Rajalingam, Nirmal Kumar Saxena. (2008) Prevalence of Cryptosporidium, Cyclospora cayetanensis and Isospora belli infection among diarrheal patients in South India. Tropical Medicine and Health 36:3, 131-136
CrossRef15
R. L. Hough. (2007) Soil and human health: an epidemiological review. European Journal of Soil Science 58:5, 1200-1212
CrossRef16
Diana K. Riner, Andrew S. Mullin, Sasha Y. Lucas, John H. Cross, H.D. Alan Lindquist. (2007) Enhanced concentration and isolation of Cyclospora cayetanensis oocysts from human fecal samples. Journal of Microbiological Methods 71:1, 75-77
CrossRef17
Guoqing Li, Shumin Xiao, Rongqiong Zhou, Weihua Li, Hicham Wadeh. (2007) Molecular characterization of Cyclospora-like organism from dairy cattle. Parasitology Research 100:5, 955-961
CrossRef18
Sabino Puente, Adolfo Morente, Teresa García-Benayas, Mercedes Subirats, Joaquín Gascón, Juan M. González-Lahoz. (2006) Cyclosporiasis: A Point Source Outbreak Acquired in Guatemala. Journal of Travel Medicine 13:6, 334-337
CrossRef19
Michael JG Farthing. (2006) Treatment options for the eradication of intestinal protozoa. Nature Clinical Practice Gastroenterology & Hepatology 3:8, 436-445
CrossRef20
T. EVERING, L. M. WEISS. (2006) The immunology of parasite infections in immunocompromised hosts. Parasite Immunology 0:0, 060607032511001-???
CrossRef21
Charles Sterling, Ynes Ortega. 2005. Outbreaks Associated with Cyclospora and Cryptosporidium. , 267-280.
CrossRef22
Kenji Kimura, Shiba Kumar Rai, Kaoru Takemasa, Yoshinobu Ishibashi, Masato Kawabata, Miodrag Belosevic, Shoji Uga. (2004) Comparison of three microscopic techniques for diagnosis of Cyclospora cayetanensis. FEMS Microbiology Letters 238:1, 263-266
CrossRef23
Athina Kansouzidou, Christina Charitidou, Themis Varnis, Norma Vavatsi, Fotini Kamaria. (2004) Cyclospora cayetanensis in a Patient with Travelers' Diarrhea: Case Report and Review. Journal of Travel Medicine 11:1, 61-63
CrossRef24
C. Dalton, A.D. Goater, J.P.H. Burt, H.V. Smith. (2004) Analysis of parasites by electrorotation. Journal of Applied Microbiology 96:1, 24-32
CrossRef25
Sarah Lean, Richard CG Pollok. (2003) Management of protozoa-related diarrhea in HIV infection. Expert Review of Anti-infective Therapy 1:3, 455-469
CrossRef26
Ynes R. Ortega, Duccio Bonavia. (2003) Cryptosporidium, Giardia, and Cyclospora in Ancient Peruvians. Journal of Parasitology 89:3, 635-636
CrossRef27
Timothy M Straub, Darrell P Chandler. (2003) Towards a unified system for detecting waterborne pathogens. Journal of Microbiological Methods 53:2, 185-197
CrossRef28
Michael J. G. Farthing. (2003) Immune response-mediated pathology in human intestinal parasitic infection. Parasite Immunology 25:5, 247-257
CrossRef29
Joan M Shields, Betty H Olson. (2003) Cyclospora cayetanensis: a review of an emerging parasitic coccidian. International Journal for Parasitology 33:4, 371-391
CrossRef30
Manju Varma, Jeff D Hester, Frank W Schaefer, Michael W Ware, H.D.Alan Lindquist. (2003) Detection of Cyclospora cayetanensis using a quantitative real-time PCR assay. Journal of Microbiological Methods 53:1, 27-36
CrossRef31
Richard Goodgame. (2003) Emerging causes of traveler’s diarrhea: Cryptosporidium, Cyclospora, Isospora, and Microsporidia. Current Infectious Disease Reports 5:1, 66-73
CrossRef32
Ynes R. Ortega, Vitaliano A. Cama, A. B. Prisma. 2003. Cyclospora: Basic Biology, Occurrence Fate and Methodologies. .
CrossRef33
Jaco J. Verweij, Daphne Laeijendecker, Eric A.T. Brienen, Lisette van Lieshout, Anton M. Polderman. (2003) Detection of Cyclospora cayetanensis in travellers returning from the tropics and subtropics using microscopy and real-time PCR. International Journal of Medical Microbiology 293:2-3, 199-202
CrossRef34
G. Alakpa, A.F. Fagbenro-Beyioku, S.C. Clarke. (2002) Cyclospora cayetanensis in stools submitted to hospitals in Lagos, Nigeria. International Journal of Infectious Diseases 6:4, 314-317
CrossRef35
C. Dalton, A.D. Goater, J. Drysdale, R. Pethig. (2001) Parasite viability by electrorotation. Colloids and Surfaces A: Physicochemical and Engineering Aspects 195:1-3, 263-268
CrossRef36
C. Olivier, S. van de Pas, P.W. Lepp, K. Yoder, D.A. Relman. (2001) Sequence variability in the first internal transcribed spacer region within and among Cyclospora species is consistent with polyparasitism. International Journal for Parasitology 31:13, 1475-1487
CrossRef37
David E. Katz, David N. Taylor. (2001) PARASITIC INFECTIONS OF THE GASTROINTESTINAL TRACT. Gastroenterology Clinics of North America 30:3, 797-815
CrossRef38
Niklaus Egloff, Thomas Oehler, Marco Rossi, Xuan M. Nguyen, Hansjakob Furrer. (2001) Chronic Watery Diarrhea Due to Co-Infection with Cryptosporidium spp and Cyclospora cayetanensis in a Swiss AIDS Patient Traveling in Thailand. Journal of Travel Medicine 8:3, 143-145
CrossRef39
A. S. Lopez, D. R. Dodson, M. J. Arrowood, P. A. Orlandi, A. J. da Silva, J. W. Bier, S. D. Hanauer, R. L. Kuster, S. Oltman, M. S. Baldwin, K. Y. Won, E. M. Nace, M. L. Eberhard, B. L. Herwaldt. (2001) Outbreak of Cyclosporiasis Associated with Basil in Missouri in 1999. Clinical Infectious Diseases 32:7, 1010-1017
CrossRef40
Barbara L. Herwaldt. (2000) Cyclospora cayetanensis: A Review, Focusing on the Outbreaks of Cyclosporiasis in the 1990s. Clinical Infectious Diseases 31:4, 1040-1057
CrossRef41
Mark L. Eberhard, Ynes R. Ortega, Darcy E. Hanes, Eva K. Nace, Rose Quy Do, Martin G. Robl, Kimberly Y. Won, Cesar Gavidia, Neil L. Sass, Keith Mansfield, Alfonso Gozalo, Jeffrey Griffiths, Robert Gilman, Charles R. Sterling, Michael J. Arrowood. (2000) ATTEMPTS TO ESTABLISH EXPERIMENTAL CYCLOSPORA CAYETANENSIS INFECTION IN LABORATORY ANIMALS. Journal of Parasitology 86:3, 577-582
CrossRef42
Jonathan D Mayer. (2000) Geography, ecology and emerging infectious diseases. Social Science & Medicine 50:7-8, 937-952
CrossRef43
Una M Morgan, Lihua Xiao, Ronald Fayer, Altaf A Lal, R.C.Andrew Thompson. (1999) Variation in Cryptosporidium: towards a taxonomic revision of the genus. International Journal for Parasitology 29:11, 1733-1751
CrossRef44
Gigi H. Brown, John C. Rotschafer. (1999) Cyclospora: Review of an Emerging Parasite. Pharmacotherapy 19:1, 70-75
CrossRef45
Ann M. Adams, Karen C. Jinneman, Ynes R. Ortega. 1999. CYCLOSPORA. , 502-513.
CrossRef46
Davide Drenaggi, Oscar Cirioni, Andrea Giacometti, Alessandro Fiorentini, Giorgio Scalise. (1998) Cyclosporiasis in a Traveler Returning from South America. Journal of Travel Medicine 5:3, 153-155
CrossRef47
Nathan M. Thielman, Richard L. Guerrant. (1998) PERSISTENT DIARRHEA IN THE RETURNED TRAVELER. Infectious Disease Clinics of North America 12:2, 489-501
CrossRef48
Robert F. Richardson, Bernd F. Remler, Bashar Katirji, M. Hatem Murad. (1998) Guillain-Barr
syndrome aftercyclospora infection. Muscle & Nerve 21:5, 669-671
CrossRef49
Rosemary Soave, Barbara L. Herwaldt, David A. Relman. (1998) CYCLOSPORA. Infectious Disease Clinics of North America 12:1, 1-12
CrossRef50
J. Meng, M. P. Doyle. (1997) EMERGING ISSUES IN MICROBIOLOGICAL FOOD SAFETY. Annual Review of Nutrition 17:1, 255-275
CrossRef51
Frederic Clayton, Carol H. Clayton. (1997) GASTROINTESTINAL PATHOLOGY IN HIV-INFECTED PATIENTS. Gastroenterology Clinics of North America 26:2, 191-240
CrossRef52
Edward A. Lew, Michael A. Poles, Douglas T. Dieterich. (1997) DIARRHEAL DISEASES ASSOCIATED WITH HIV INFECTION. Gastroenterology Clinics of North America 26:2, 259-290
CrossRef53
Herwaldt, Barbara L., Ackers, Marta-Louise, the Cyclospora Working Group. (1997) An Outbreak in 1996 of Cyclosporiasis Associated with Imported Raspberries. New England Journal of Medicine 336:22, 1548-1556
Full Text54
J. Logar, M. Polj
sak-Prijatelj, A. Andlovic. (1997) Cyclospora cayetanensis, potential cause of diarrhoea. Journal of Infection 34:3, 284-285
CrossRef55
F. Petry, J. Hofstätter, M. Jung, B. K. Schulz, G. Deitrich, P. Schirmacher. (1997) Cyclospora cayetanensis: First imported infections in Germany. Infection 25:3, 167-170
CrossRef56
Stuart R. Framm, Rosemary Soave. (1997) AGENTS OF DIARRHEA. Medical Clinics of North America 81:2, 427-447
CrossRef57
Rayhan Hashmey, Robert M. Genta, A. Clinton White. (1997) Parasites and Diarrhea. I: Protozoans and Diarrhea. Journal of Travel Medicine 4:1, 17-31
CrossRef58
Tania M. Schubach, Elizabeth S. Neves, Ana C. Leite, Abelardo Q.-C. Araújo, Hércules de Moura. (1997) Cyclospora cayetanensis in an asymptomatic patient infected with HIV and HTLV-1. Transactions of the Royal Society of Tropical Medicine and Hygiene 91:2, 175
CrossRef59
Ted S. Steiner, MD, Nathan M. Thielman, MD, Richard L. Guerrant, MD. (1997) PROTOZOAL AGENTS: What Are the Dangers for the Public Water Supply?. Annual Review of Medicine 48:1, 329-340
CrossRef60
ANNE-MARIE DELUOL, MARIE FRANCOISE TEILHAC, JEAN-LOUIS POIROT, FRANCOISE. HEYER, LAURENT BEAUGERIE, FRANCOIS-PATRICK. CHATELET. (1996) Cyclospora sp :Life Cycle Studies in Patient by Electron-Microscopy. The Journal of Eukaryotic Microbiology 43:5, 128S-129S
CrossRef61
Sathaporn Manatsathit, Somsit Tansupasawasdikul, Darawan Wanachiwanawin, Surachai Setawarin, Parvinee Suwanagool, Saranjit Prakasvejakit, Somchal Leelakusolwong, Boonchuey Eampokalap, Udom Kachintorn. (1996) Causes of chronic diarrhea in patients with AIDS in Thailand: A prospective clinical and microbiological study. Journal of Gastroenterology 31:4, 533-537
CrossRef62
S. C. Clarke, M. McIntyre. (1996) The incidence of Cyclospora cayetanensis in stool samples submitted to a district general hospital. Epidemiology and Infection 117:01, 189
CrossRef63
Wood, Alastair J.J., , Liu, Leo X., Weller, Peter F., . (1996) Antiparasitic Drugs. New England Journal of Medicine 334:18, 1178-1184
Full Text64
Sarah M. Paget, John M. Goldsmid, Jim M.B. Wane. (1995) Intestinal Parasitic Infections of Refugees in Tasmania. Journal of Travel Medicine 2:4, 267-268
CrossRef65
Adeleh Ebrahimzadeh, Linda Rogers. (1995) Diarrhea caused by aCyanobacterium-like organism. European Journal of Epidemiology 11:6, 661-664
CrossRef66
R. Himy, O. Villard, M. Kremer. (1995) Cyclosporidia: A General Review. Journal of Travel Medicine 2:1, 33-36
CrossRef67
C.W. Hoge, P. Gaudio, P. Echeverria, D.R. Shlim, J.G. Rabold, P. Pandey, A. Walch, R. Rajah, M. Ghimire. (1995) Placebo-controlled trial co-trimoxazole for cyclospora infections among travellers and foreign residents in Nepal.. The Lancet 345:8951, 691-693
CrossRef68
Rosemary Soave, WarrenD. Johnson. (1995) Cyclospora: conquest of an emerging pathogen. The Lancet 345:8951, 667-668
CrossRef69
A. González-Ruiz, R.P. Bendall. (1995) Size matters: the use of the ocular micrometer in diagnostic parasitology. Parasitology Today 11:2, 83-85
CrossRef70
Joaquim Gascon, Manuel Corachan, Josep Antoni Bombi, Maria Eugenia Valls, Josep Maria Bordes. (1995) Cyclospora in Patients with Traveller's Diarrhea. Scandinavian Journal of Infectious Diseases 27:5, 511-514
CrossRef71
IRINA ECKARDT. (1994) Challenging Complexity Conceptual Issues in an Approach to New Disease. Annals of the New York Academy of Sciences 740:1 Disease in Ev, 408-417
CrossRef72
J.Gregory Rabold, CharlesW. Hoge, DavidR. Shlim, Carol Kefford, Ramachandra Rajah, Peter Echeverria. (1994) Cyclospora outbreak associated with chlorinated drinking water. The Lancet 344:8933, 1360-1361
CrossRef73
P.L. Chiodini. (1994) A ‘new’ parasite: human infection with Cyclospora cayetanensis. Transactions of the Royal Society of Tropical Medicine and Hygiene 88:4, 369-371
CrossRef74
Glynis A. Grigoriew, Sharon Walmsley, Lillian Law, Sinn Lim Chee, James Yang, Jay Keystone, Mel Krajden. (1994) Evaluation of the merifluor immunofluorescent assay for the detection of Cryptosporidium and Giardia in sodium acetate formalin-fixed stools. Diagnostic Microbiology and Infectious Disease 19:2, 89-91
CrossRef75
Herbert L. DuPont, Fida M. Khan. (1994) Travelers' Diarrhea: Epidemiology, Microbiology, Prevention, and Therapy. Journal of Travel Medicine 1:2, 84-93
CrossRef76
DAVID W. CHUI, ROBERT L. OWEN. (1994) AIDS and the gut. Journal of Gastroenterology and Hepatology 9:3, 291-303
CrossRef77
M.John Albert, Iqbal Kabir, Tasnim Azim, Anowar Hossain, Mohammad Ansaruzzaman, Leanne Unicomb. (1994) Diarrhea associated with Cyclospora sp. in Bangladesh. Diagnostic Microbiology and Infectious Disease 19:1, 47-49
CrossRef78
H. L. DuPONT. (1994) Review article: infectious diarrhoea. Alimentary Pharmacology & Therapeutics 8:1, 3-13
CrossRef79
(1993) Cyanobacterium-Like Cyclospora Species. New England Journal of Medicine 329:20, 1504-1505
Full Text80
Guillermo Madico, RobertH. Gilman, Elba Miranda, Lilia Cabrera, CharlesR. Sterling. (1993) Treatment of cyclospora infections with co-trimoxazole. The Lancet 342:8863, 122-123
CrossRef81
C.W. Hoge, P. Echeverria, D.R. Shlim, R. Rajah, M. Shear, J.G. Rabold, J. Triplett. (1993) Epidemiology of diarrhoeal illness associated with coccidian-like organism among travellers and foreign residents in Nepal. The Lancet 341:8854, 1175-1179
CrossRef
- Letters
