Acta Tropica 115 (2010) 181193

Contents lists available at ScienceDirect

Acta Tropica

journa l homepage: www.e lsev ier .com/ locate /ac ta t ropica

Review

Epidem

Leonor CPostgrado de In

a r t i c l

Article history:Received 23 DAccepted 1 ApAvailable onlin

Keywords:Cyclospora cayCyclosporiasisEpidemiologyRisk factorsTransmissionReview

2010 Elsevier B.V. All rights reserved.

Contents

1. Introd1.1.1.2.1.3.

2. Biolog2.1.2.2.2.3.2.4.2.5.

3. Epide3.1.3.2.3.3.3.4.3.5.3.6.

4. Preve

Fax: +58 2E-mail add

0001-706X/$ doi:10.1016/j.uction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182Historical perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182Human cyclosporiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182Aim of this review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182Current taxonomy and phylogeny . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182Life cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183Structure and survival of the infective stage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183Infectivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183Environmental occurrence of oocysts and transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184

miology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184Distribution of human cyclosporiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184Geographic distribution and prevalence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185Age and sex distribution. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186Seasonal distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187Reservoirs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187Sources and routes of transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1873.6.1. Waterborne transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1873.6.2. Foodborne transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1883.6.3. Soil transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1883.6.4. Zoonotic transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1893.6.5. Airborne transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189

ntion and control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189

61 7597247.ress: leonorbonilla42@yahoo.com.

see front matter 2010 Elsevier B.V. All rights reserved.actatropica.2010.04.001iology of Cyclospora cayetanensis: A review focusing in endemic areas

hacn-Bonilla

munologa, Instituto de Investigaciones Clnicas, Facultad de Medicina, Universidad del Zulia, Apartado Postal 23, Maracaibo, Venezuela

e i n f o

ecember 2009ril 2010e 9 April 2010

etanensis

a b s t r a c t

Cyclospora cayetanensis is an intestinal coccidian protozoon that has emerged as an important causeof endemic or epidemic diarrhoeal illness in children and adults worldwide. Humans appear to be theonly natural hosts. However, the role of animals as natural reservoirs is uncertain but of increasingconcern. Human-to-human spread of the parasite occurs indirectly via the environment through oocystsin contaminated water, food or soil. In endemic areas, risk factors associated with the infection includecontaminatedwater or food, contactwith soil or animals, typeof sanitation and lowsocioeconomic status.Infections linked to soil contact provide reasons to believe that this route of spreadmay bemore commonthan realised in disadvantaged community settings. C. cayetanensis is an important cause of travellersdiarrhoea and numerous large foodborne outbreaks associated with the globalisation of the food supplyand importation of fruits and vegetables fromdeveloping countries have occurred.Waterborne outbreakshave also been reported. Implementation of measures to prevent or control the spread of Cyclosporaoocysts in the environment is critical. In endemic areas, themost important steps to prevent infection areimproving environmental sanitation and health education. Signicant gaps remain in our understandingof the epidemiology of human cyclosporiasis that highlight the need for continued research in severalaspects of C. cayetanensis.

182 L. Chacn-Bonilla / Acta Tropica 115 (2010) 181193

5. Future perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1896. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190

1. Introdu

1.1. Histori

Coccidialar apicompthe intestin(Lainson, 20namedby Sericola in min inverteblife cycle wCyclospora sinsectivorescurrently 1

Cyclospopatients frococcidium,Subsequentdiarrhoea, mwere publial., 1990;cyanobactbecause ofof theblue-of this orgaquently, thin Peru andbecause whtwo sporocnamedC. casignicantlalso in its othan oblongpitheci, C. coocyts seeminsectivoresthose that ispherical oo

1.2. Human

Cyclosporhoea worldIn immunorhoea is cominjury and2003). In dwith caseslated from tSoutheast AMcIntyre, 12004; Bouret al., 2008as a signicrecognisedrhoeal illnefoodproducthe developHerwaldt a

Dawset aStatstralShlimMans6, 20or toa les5; Develcasell deravendem199ar, 2007pidepoo

m of

s papiolo

ies anerstar to ievenstic are se

s (Ebjadh

logy

ic knto

on aies.

rren

ayetaicomidaethe

erreded fdiumativee seq(SSUrimAdamtanesionrasitection

cal perspective

n protozoa of genus Cyclospora are obligate intracellu-lexan parasites that infect the mucosal epithelium ofe or bile duct of a variety of hosts, mostly vertebrates05). The genus Cyclospora was rst characterised and

chneider (1881),who recognised and identied C. glom-illipedes. This appears to be the only species found

rates. Subsequently, C. caryolytica was named and itsas described (Schaudinn, 1902). Since this time, severalpecies have been described in reptiles, mostly snakes,, rodents and primates, including humans. There are

9 recognised species (Lainson, 2005).ra was rst identied as a human pathogen in threem Papua, New Guinea but it was thought to be aprobably a new species of Isospora (Ashford, 1979).ly, several reports on similar ndings in patients withostly travellers to endemic areas and AIDS patients,

shed (Soave et al., 1986; Hart et al., 1990; Long etShlim et al., 1991; Wurtz et al., 1993). The termerium-like bodies was proposed for the organisman ultrastructural resemblance to unicellular membersgreenalgae (Longet al., 1991). Later, the coccidial naturenism was pointed out (Bendall et al., 1993). Subse-

e parasite was described from human faecal materialwas identied as a coccidian of the genus Cyclosporaen the oocysts were induced to sporulate, they yieldedysts, each containing two sporozoites. The parasite wasyetanensis (Ortegaet al., 1993, 1994). This speciesdiffersy fromall otherCyclospora speciesnotonly in itshostbutocyst stage, which is much smaller and spherical rather. The recovery from non-human primates of C. cerco-

olobi and C. papionis that produce also small, sphericals to suggest twodifferent groupings: species that infectand rodents and produce large, oblong oocysts and

nfect primates, including humans, and produce small,cysts (Eberhard et al., 1999a).

cyclosporiasis

ra cayetanensis is an important emerging cause of diar-wide that leads to signicant morbidity and mortality.

competent hosts, mild-to-moderate, self-limiting diar-mon. In immunocompromised hosts, severe intestinal

prolonged diarrhoea is observed (Shields and Olson,eveloped countries, the disease has been associatedof travellers diarrhoea; the parasite is commonly iso-ravellers to Latin America, the Indian subcontinent andsia (Long et al., 1990; Shlim et al., 1991; Clarke and996; Drenaggi et al., 1998; Manseld and Gajadhar,e et al., 2006; Puente et al., 2006; Ramrez-Olivencia). However, the coccidium has only been documentedant human pathogen in the early 1990s when it wasas the causative agent of numerous outbreaks of diar-ss in the developed world, mostly associated with freshe, such as soft fruits and leafy vegetables imported from

2000;(HuangUnitedandAuareas (1998;al., 200watertion toal., 199

In dfor theare wetional tfrom eBeach,Gajadh2006, 2other eremain

1.3. Ai

Thiepidemcountrto undin ordeandprdiagnoThere aaspectand Ga

2. Bio

Bascrucialinfectistrateg

2.1. Cu

C. clumApEimeriWithinera refdescribtospori

Relor genrRNAusing prRNA (C. cayeconcluian paing world (Chambers et al., 1996; Anonymous, 1997;nd Ackers, 1997; Herwaldt and Beach, 1999; Herwaldt,

SSU-rRNA slogenetic tron, 2005). Waterborne disease has also been identiedl., 1995; Dawson, 2005; Karanis et al., 2007). Unlike thees and Canada, most cases of cyclosporiasis in Europeia have been linkedwith international travel in endemicet al., 1991; Clarke andMcIntyre, 1996; Drenaggi et al.,

eld and Gajadhar, 2004; Puente et al., 2006; Boure et07). Exposure to contaminated drinking or recreationalsewage have been involved in the spread of the infec-ser extent (Wurtz et al., 1993; Hale et al., 1994; Ooi etawson, 2005).oped nations, the risk factors andmodes of transmissions of cyclosporiasis that have been identied and studiedned. Most of the cases have been related to interna-l or to foodborneoutbreaks causedby importedproduceic regions (Herwaldt and Ackers, 1997; Herwaldt and

9; Herwaldt, 2000; Gascon et al., 2001; Manseld and004; Dawson, 2005; Puente et al., 2006; Boure et al.,). In contrast, the risk factors and routes of spread andmiologic features for C. cayetanensis in developing areasrly understood.

this review

er reviews the current status of knowledge of thegy of human cyclosporiasis, focusing in developingdemphasising featuresof theparasite that areessentialnding the surveillance and risk factors for the infection,nstitute appropriate risk management, control systemstionof transmission.A reviewof thepathogenic, clinical,nd therapeutic features of the infection is not provided.veral major reviews that have described in detail theseerhard et al., 1997; Shields and Olson, 2003; Manseldar, 2004).

owledge of the biologic features of C. cayetanensis isunderstanding the complex epidemiology of humans well as the difculty to develop successful control

t taxonomy and phylogeny

nensis is taxonomically classied as follows: subphy-plexa, subclass Coccidiasina, order Eucoccidiorida, family(Sterling and Ortega, 1999; Shields and Olson, 2003).subphylum Apicomplexa there are several related gen-to collectively as coccidia including ve that have beenrom humans: Sarcocystis, Toxoplasma, Isospora, Cryp-and Cyclospora (Ortega et al., 1994).

ly little is known regarding the genome organisationuences of C. cayetanensis. However, the small-subunit-rRNA) sequence was obtained by PCR amplicationers based on the highly conserved regions of the SSU-

et al., 2000). Analysis of this sequence revealed thatnsis is closely related to Eimeria spp. and supports thethat both genera belong to the same family of coccid-s (Relman et al., 1996). The inclusion of an additional

equence of E. falciformis, a parasite of mice, in the phy-ee claried the resolution of the tree into three different

L. Chacn-Bonilla / Acta Tropica 115 (2010) 181193 183

clades:mammalian Eimeria, avian Eimeria and Cyclospora. With theaddition of molecular data of more species, particularly the speciesof Cylospora described from mammals other than primates, it maybe reasonably to consider reclassifying the Cyclospora of primates,including ha new genuSSU-rRNA sof Cyclospor1999). C. calower primsingle branria (EberharCyclosporaclosely relainfect huma

2.2. Life cyc

C. cayetacycle not fuing a singleasexual andal., 1996; Ocomplex ancidia, whichmeronts, azygotes, an

The lifestage, theing infectivsmall intestzoites and sa supranucvacuoles (Szoites whicmeronts whType Imeroand form terated, thesby differen(macrogammicrogamezygote. A rdevelops inNhieu et al.tually, thesporont divzoites (Ortsporulationto weeks, dment into tUnder expeusing 2.5%in 713 day(Ortega et a

2.3. Structu

Oocysts7.79.9mopen and ohave variabnot stain atrescence illor green unal., 1993; S

microscopy studies, a sporulated oocyst is described as possessinga two-layered oocyst wall (63 and 50nm thick, respectively) sur-rounding twosporocysts, eachwith62-nm-thickwalls surroundinga plasma membrane. Sporocyst has Stieda and substieda bodies

residoitescidianmenntale, 200endef infeora oays (ucedg at 6ma

er trre ve(Lon

ate teaterian oeriaora,trea

nensise ofd Leor ofocysy anmateubstlacedto 4d noanarasingk ofC cayg fors chl

fectiv

actuon dia, it, 199s (Adoocytooda wids (Ad virogenhumarst inifferece ossibby m

ions nvironumans, and either the bird or mammalian Eimeria tos (Eberhard et al., 1999a). It has been suggested thatequences of Isospora should be compared with thosea to help clarify taxonomic issues (Sterling and Ortega,yetanensis and the recognised Cyclospora spp. infectingates (C. cercopitheci, C. papionis, and C. colobi) group as ach intermediate between mammalian and avian Eime-d et al., 1999a). It is not yet known whether all humanisolates belong to the same species and whether theted Cyclospora species described from lower primatesns.

le

nensis is an obligate intracellular parasite with a lifelly characterised. It appears to be monoxenous, requir-human host to complete the entire life cycle, since bothsexual stages have been observed in this host (Sun et

rtega et al., 1997a; Connor et al., 1999). The life cycle isd follows the patterns described for other enteric coc-involves a merogonic cycle with two generations of

gametogonic cycle with macro- and microgametes andd a sporogony (Schaudinn, 1902).cycle begins upon the ingestion of the transmissiblesporulated oocyst, which excysts in the gut releas-e sporozoites. These invade the epithelial cells of theine (Sun et al., 1996; Ortega et al., 1997a). The sporo-ubsequent stages are located within the cytoplasm inlear position and are surrounded by parasitophorousun et al., 1996). The sporozoites transform into tropho-h undergo asexual proliferation by merogony to formich contain merozoites. Two types of meronts develop.nts contain 812merozoiteswhich penetrate host cellsype II meronts containing four merozoites. Once lib-e merozoites enter host cells and start sexual phasetiating into either male (microgametocyte) or femaleetocite) stages. The former forms numerous agellatedtes. The fertilised macrogametocite develops into aesistant wall is then formed around the zygote andto an oocyst which contains the sporont (Tran Van, 1996; Ortega et al., 1997a; Connor et al., 1999). Even-unsporulated oocysts are passed in the stool and theides into two sporocysts, each containing two sporo-ega et al., 1994). The environmental conditions forare not yet fully understood. Oocysts require a fewdaysepending on climatic factors, to mature in the environ-he infective sporulated oocysts (Ortega et al., 1998).rimental conditions, sporulation has been carried outpotassium dichromate (Ortega et al., 1993) and occurss at temperatures between 22 and 32 C within 14 daysl., 1998).

re and survival of the infective stage

are small and spheroidal in shape with a diameter of. With the modied acid-fast stain, some oocysts arethers not opened to the stain. Some stain dark red andle number of dark inclusion bodies, whereas others doall and appear as transparent spheres. Under epiuo-umination, they have the ability to autouoresce blueder a 365nm or a 490nm dichromatic lter (Ortega etterling and Ortega, 1999). From transmission electron

and asporoz

CocenviroronmeBehnkfor extality oCyclospfor 7 dbe indheatintant toin watthey a15minmoderthat wcoccid

EimCyclospnationcayetaat a do(Lee anindicatlated oin dairdichrodairy swere pfor uption di(Sathyprocesthe ris2007).heatingaseou

2.4. In

ThebasedcoccidOrtegaoocystnensisunderssite inhumantors ana pathinfectin thefromdexistenit is poterisedconditthe enuum with spherical globules. Each sporocyst has two(Ortega et al., 1993, 1994).oocysts can persist for long periods of time in thet, maintaining their infectivity even under harsh envi-

conditions (Manseld and Gajadhar, 2004; Sinski and4). Naturally occurring Cyclospora oocysts may survive

d periods in the environment, given themarked season-ction in endemic regions (Herwaldt and Beach, 1999).ocysts survive inwater at 4 C for 2months and at 37 CSmith et al., 1997; Ortega et al., 1998). Oocysts cannotto sporulate after freezing at 18 C for 24h and after0 C for 1h (Sterling and Ortega, 1999). They are resis-

ny disinfectants, including chlorination at levels usedeatment (Rabold et al., 1994; Soave et al., 1998), butry sensitive to desiccation; oocyst wall ruptures afterg et al., 1991). The oocysts require time, moisture andmperature to become infective. It has been establishedfacilitates both the development and transmission ofocysts (Manseld and Gajadhar, 2004).acervulina, a chicken coccidium with similarities tohas been used as a surrogate to develop decontami-tments for fruits imported from endemic areas for C.s. Freezing and heat treatment and gamma irradiation,1.0 kGy or higher, were effective against the coccidiume, 2001). Sporulation of C. cayetanensis oocysts, as anviability, has been determined on produce. Unsporu-ts were subjected to freezing and heating conditionsd basil substrates and then placed in 2.5% potassium. Sporulation occurred when oocysts resuspended inrates were stored at 15 C within 24h and when theyinwater or basil at 20 C for up to two days and at 37 C

days. Few oocysts sporulated at 50 C for 1h. Sporula-t occur at 70, 70, and 100 C in water or basil leavesyanan and Ortega, 2006). High-hydrostatic-pressureand UV light radiation have been suggested to reducecyclosporiasis associated with produce (Kniel et al.,etanensis sporulation was not affected after microwaveup to 45 s (Ortega and Liao, 2006) and after the use oforine dioxide at 4.1mg/l for 20min (Ortega et al., 2008).

ity

al infectious dose of Cyclospora oocysts is unknown butata from outbreak studies and extrapolations to otheris generally thought to be relatively low (Sterling and9; Dixon et al., 2005), probably between 10 and 100am and Ortega, 1999). Factors that allow C. cayeta-sts become infectious in the environment are not fully. Researchers have been unable to establish the para-e variety of animal models (Eberhard et al., 2000) and

lfano-Sobsey et al., 2004). Host susceptibility, risk fac-ulence are factors that inuence the host response toexposure. Virulence and features of the coccidium ton hosts are unknown. Nucleotide sequence variabilityternal transcribed spacer regionswithinC. cayetanensisnt geographic areas has beenobserved and suggests thefmultiple strains (Adamet al., 2000;Olivier et al., 2001);le that many human Cyclospora infections are charac-ulticlonality of the infecting coccidia. The triggers andecessary for Cyclospora oocysts to become infectious inment are not fully understood.

184 L. Chacn-Bonilla / Acta Tropica 115 (2010) 181193

Table 1Biologic and epidemiologic features of Cyclospora cayetanensis that are relevant toits epidemiology.

Feature Epidemiologic signicance

Relative small size Difcult to lterResistent, chlorine oocysts Spread in chlorinated water or

swimming poolsLikely, low infective dose Easily acquiredProbably, humans are the

only hostLikely, lack of zoonoticpotential

Oocysts shed innon-infective form

Person-to-person transmissionis highly unlikely

Oocysts need externalmaturation

A vehicle of transmission isneeded

Marked seasonality Oocysts survive for longperiods in the environment

Environmental dispersalcan contaminate water,food and soil

Widely spread withwater-food-soilbornetransmission

2.5. Environmental occurrence of oocysts and transfer

Little information is available on C. cayetanensis in the environ-ment and in animal population. The parasite has been detected onfresh vegetables from markets in Peru (Ortega et al., 1997b) andCosta Rica (Calvo et al., 2004), and from farms in Nepal (Sherchandand Cross, 2001). The relationship between numbers of organismsfound on fresh produce and numbers in the environments in whichcrops were grown is unclear (Dawson, 2005). In Egypt, the coccid-ium was identied in bivalves from markets in Alexandria (Negm,2003).C. cayetanensiswasdescribed indrinkingwater inGuatemala

(Dowd et al., 2003) and Nepal (Rabold et al., 1994). In Vietnam, theparasite was identied in drinking water and in 63.6% of rivers andlakes samples (Miegeville et al., 2003). In Egypt, the coccidium wasisolated in ve residential areas from several water sources usedfor consumption, such as a drain, an irrigation canal, undergroundwater and piped water, reecting the high environmental contam-ination of the area (El-Karamany et al., 2005). In other study, theparasite was observed in 0.24% of 840 potable water samples fromsevendistricts (Elshazly et al., 2007). InPer, (Sturbaumet al., 1998)and Nepal (Sherchand and Cross, 2001), Cyclospora oocysts weredetected in sewage water. Since there is little or no monitoring forCyclospora in the environment, it is unknown whether the parasiteis widespread.

Critical to the epidemiology and transmission of C. cayetanensisare some biologic and epidemiologic features that determine themedical and public health importance of this coccidium. These arepresented in Table 1 and discussed below.

3. Epidemiology

3.1. Distribution of human cyclosporiasis

As a result of the increased awareness of infection andthe development of diagnostic screening techniques, widespreadinvestigation of the frequency of cyclosporiasis has ensuedthroughout the world. C. cayetanensis infection has been describedworldwide, in developed and developing countries and in urbanand rural areas (Ortega et al., 1998; Shields and Olson, 2003).However, prevalence rates of Cyclospora are often underestimated

Table 2Prevalence of Cyclospora cayetanensis, in immunocompetent individuals from developing countriesa.

Country Population Infected % (no./no. tested) Controls % (no./no. tested) References

Mexico Children 3.3 (18/541) NRb Bernal Redondo et al. (1998)Guatemala All ages 2.3 (126/5552) NR Bern et al. (1999)Honduras All ages 2.0 (96/4698) NR Kaminsky (2002)Brazil Adults 0.3 (14/4869) NR Do Nascimento et al. (2005)Peru All ages 0.7 (2/272) NR Rodriguez-Alarcn et al. (2007)

All ages 7.8 (7/90) 0 (0/50) Zerpa et al. (1995)NR Burstein Alva (2005)NR

Venezuela NRCuba 0 (0/2

NR

Turkey 0 (0/3NR

Jordan NRSaudi Arabia 4.2 (8China 0.2 (1Nepal 2.0 (2

NR

Bangladesh

Lao PDRThailand

IndonesiaEgypt

NigeriaUgandaKenyaTanzaniaMozambiqu

a Based on cb Not reportAll ages 7.3 (217/2968)Children 13.0 (64/489)

Children 5.3 (7/132)07 yr 4.4 (5/113)Children 0.2 (20/7956)

All ages 0.5 (23/4660)All ages 0.4 (2/554)

All ages 6.0 (12/200)

L. Chacn-Bonilla / Acta Tropica 115 (2010) 181193 185

Table 3Prevalence of Cyclospora cayetanensis in immunocompromised individuals from developing countriesa.

Country Population Infected % (no./no. tested) Controls % (no./no. tested) References

Guatemala Malnourished children 0.9 (1/111) NRb Pratdesaba et al. (2001)NR

Honduras NRNR

Colombia NRVenezuela NR

3.4 (

Brazil NRCuba 0 (0

NR

Haiti NRNR

China 0.2 (India 0 (0

NR0 (0

Thailand NRIndonesia NREgypt NR

2.8 (

Cameroon NRKenya NRTanzania NR

0 (0

Zimbabwe NR

a Based on cb Not reportc PCR metho

because ofthe fact thatintermittenlimitations.imens by teare subjectestudies havwith gastroor seek meto diagnosttoward chilfrom gastroDespite thethe ubiquitwide, and man epidemi

3.2. Geogra

From aviduals fromthem withage 1.7%), wcontrols varsuggest tha3340 immuwith diarrhestimates t(average 4.infections mand immunability of ththe microscreports in A

he exon raomisragethafor mHIV/AIDS patients 3.8 (6/157)

HIV patients 6.8 (9/133)AIDS patients 3.6 (2/56)

1063 yr 2.6 (1/38)AIDS adults 9.8 (7/71)HIV adults 6.8 (5/74)

Immunocompromised patients 1.0 (5/393)AIDS adults 3.0 (2/67)HIV adults 3.5 (6/170)

HIV adults 11.3 (51/450)AIDS adults 36.0 (27/74)c

Immunocompromised patients 9.4 (3/32)HIV adults 1.0 (1/100)HIV adults 0 (0/298)HIV adults 2.9 (1/113)

AIDS adults 2.2 (1/45)HIV/AIDS adults 4.4 (14/318)Immunocompromised patients 4.0 (6/150)Malnourished children 5.6 (2/36)

HIV adults 0 (0/154)HIV adults 0 (0/88)AIDS patients 1.2 (1/86)HIV children 2.6 (1/38)

HIV adults 0 (0/88)

onventional faecal examination.ed.d.

the low sensitivity of conventional detection methods,theparasitemaybepresent at subclinical levels and thet nature of oocysts shedding. Surveys have had severalTheyhavedependedonevaluationof single faecal spec-chniques that might have missed light infections andd to variable levels of technical expertise. Most of the

with tinfecticompran avetulatedchoicee been based on selective populations, such as patientsintestinal symptoms or diarrhoea who are hospitaliseddical attention or simply on faecal samples submittedic laboratories. The resulting survey data may be biaseddren since medical intervention is more likely to resultintestinal symptoms appearing in younger patients.

se limitations, surveysprovidevaluabledata concerningous nature of infection in various populations world-ay detect changing trends and signal the probability of

c.

phic distribution and prevalence

review of 47,642 apparently immunocompetent indi-endemic areas attending health care centres, most of

diarrhoea, infection rates ranged from 0 to 13% (aver-hereas the isolation rates from matched asymptomaticied from 0 to 4.2% (average 0.4%) (Table 2). The surveyst C. cayetanensis is associated with diarrhoea. Amongnocompromised persons, mostly HIV/AIDS patients

oea, the percentages of Cyclospora infections presentedhat differ from one another, ranging from 0 to 36%5%) (Table 3). Variations in prevalence of Cyclosporaay be inuenced by study design, geographic area, ageologic status of the population studied, seasonal vari-e parasite, methods of detection used, and expertise ofopist. It is interesting to note the scarcity of Cyclosporafrican populations. In immunocompetent individuals,

parasite (EbIn comm

(average 4.2tion rate (4endemic htion of theof asymptonoted. Infecmild illnesset al., 1999settings, C.role. It apperal populacentre popwith diarrhal., 1999; Aand Gajadhcommon inexposure mtomatic excal., 2002). Inlihood of dinfection (B

The preving countriin local resition in thes1999; CedePratdesaba et al. (2001)

Kaminsky (1997)Kaminsky et al. (2007)

Arzuza et al. (2003)Chacn-Bonilla et al. (2001)

1/29) Chacn-Bonilla et al. (2006)

De Souza and Garca Zapata (2006)/136) Escobedo and Nunez (1999)

Capo de Paz et al. (2003)

Pape et al. (1994)Raccurt et al. (2008)

1/400) Wang et al. (2002)/50) Kumar et al. (2002)

Becker et al. (2007)/113) Gupta et al. (2008)

Manatsathit et al. (1996)Kurniawan et al. (2009)Abou el Naga (1999)

1/36) Rizk and Soliman (2001)

Sarfati et al. (2006)Gatei et al. (2006)Cegielski et al. (1999)

/20) Cegielski et al. (1999)

Gumbo et al. (1999)

ception of one study (Nassef et al., 1998), very lowtes of 1% have been observed (Table 2). In immuno-edpersons, prevalences of 05.6%have been foundwithpercentage of 1.6% (10/640) (Table 3). It has been pos-t the amount of sulpha drugs administered as drugs ofalaria and other infectious diseases may suppress the

erhard and Arrowood, 2002).unity based studies, prevalence rates from 0 to 41.6%%) have been found (Table 4). Whether the high infec-1.6%) observed in a Peruvian community reects an

igh risk of exposure to the parasite by the popula-area or an epidemic is not known. High percentagesmatic carriers (68.298.7%, average 87.1%) have beented children are often asymptomatic or have relatively(Madico et al., 1997; Ortega et al., 1997a; Eberhard

b; Chacn-Bonilla et al., 2003, 2007). Thus, in endemiccayetanensis may not play a consistently pathogenicears that in endemic areas, the situation at the gen-tion level is quite different than that observed in healthulations in whom a strong association of the parasiteoea has been recognised (Zerpa et al., 1995; Fryauff etl-Braiken et al., 2003; Nunez et al., 2003; Manseldar, 2004). This nding suggests that cyclosporiasis isimpoverished areas and that very early and persistentay be associated with immunity to illness and asymp-retion (Madico et al., 1997; Ortega et al., 1997a; Bern etfact, after an initial episode of cyclosporiasis, the like-

iarrhoea decreases signicantly with each subsequentern et al., 2002).alence of C. cayetanensis is unknown in some develop-es. However, the reports of sporadic cases of infectiondents or foreign visitors reect the endemicity of infec-e nations. Such is the case of Costa Rica (Chinchilla et al.,no, 2002), Argentina (Velasquez et al., 2004), Dominican

186 L. Chacn-Bonilla / Acta Tropica 115 (2010) 181193

Table 4Prevalence of Cyclospora cayetanensis in communities from developing countriesa.

Country Population Infected % (no./no. tested) Asymptomatic % (no./no. tested) References

Mexico Children 3.3 (9/272) NRb Daz et al. (2003)Guatemala Raspberry farm workers and family members 3.3 (6/182) NR Bern et al. (1999)

Raspberry farm workers 0 (0/206) NR Pratdesaba et al. (2001)

Venezuela All ages 6.1 (13/212) 84.6 (11/13) Chacn-Bonilla et al. (2003)All ages (Indians) 11.9 (19/160) 98.7 (158/160) Devera et al. (2005)All ages 8.3 (43/515) 86.0 (37/43) Chacn-Bonilla et al. (2007)

Peru 02.6 yr 10.9(41/377) 73.2 (30/41) Ortega et al. (1993)Children 1.1 (63/5836) 68.2 (43/63) Madico et al. (1997)All ages 41.6 (121/291) NR Burstein Alva (2005)Children 2.6 (22/845) NR Perez Cordn et al. (2008)Adults 4.3 (11/256) NR Roldan et al. (2009)

Brazil All ages (Indians) 10.8 (9/83) NR Das Borges et al. (2009)

Haiti Children and mothers 7.9 (59/741) 86.8 (46/53) Eberhard et al. (1999b)All ages 6 (24/402) NR Lpez et al., 2003

a Based on conventional faecal examination.b Not reported.

Republic (Green et al., 2000; Estran et al., 2004), Bangladesh (Albertet al., 19941979),Moroet al., 2007)et al., 2000the patientrespectively

Occurrenreported inHerwaldt, 2al., 2005). Wited (Tablewith detecof them haexplained bsure of natal., 1997; Obeen demooccur in thve have b(Table 5). Orecords (Dodemics in loareas is notal., 2006) oof the paraleaving somupper socia

explain the limited outbreaks of cyclosporiasis reported in endemicre th

nensiing end ipro

babi

e an

devee imell kortalIV ine relexp

DrenBour5).lospostudihav

spitalinicaoccur997;2). In

Table 5Outbreaks of c

Country

Nepal

Indonesia

MexicoBrazilColombiaGuatemalaPeru

a Based on cb Unknown.c PCR metho), Vietnam (Naito et al., 2009), New Guinea (Ashford,cco (Kansouzidou et al., 2004) andMadagascar (Boure. In Chile (Madrid et al., 1998) and Uruguay (Salvatella), one case was reported from each country. However,s presented cyclosporiasis after visiting Cuba or Peru,, that are endemic areas.ce of C. cayetanensis outbreaks has mostly beenthe developed world (Herwaldt and Beach, 1999;000; Ho et al., 2002; Doller et al., 2002; Hoang ethereas their occurrence in endemic settings are lim-

5). Only, 11 outbreaks appear to have been publishedtion of infection in 10.386% of diarrhoeal cases. Sixve involved foreign residents or visitors. This may bey the protective immunity induced by repeated expo-ives from endemic regions to the parasite (Madico etrtega et al., 1997a; Bern et al., 2002). However, it hasnstrated recently that outbreaks of cyclosporiasis doe developing world among local populations. At leasteen published from Mexico, Brazil, Colombia and Peruther three from Brazil have been reported in ofcialNascimento et al., 2005). The explanation for these epi-cal adult populations is that acquired immunity in theselong lasting and fades over time (Torres-Slimming et

r that geographic distribution, prevalence and spreadsite in one region may vary from one place to anothere populations unprotected, particularly those from thel class (Mundaca et al., 2008). Other factors that could

areas acayetaSlimmareas awith imthe pro

3.3. Ag

InincludIt is wand mwith Hness arAmong1996;2006;(Table

Cycof thediseaseics, howith crhoeaet al., 1al., 200yclosporiasis in developing countriesa.

Year Population Disease cases Infected % (no.)

1989 Foreigners 535 10.3 (55)1989 Foreigners 14 86.0 (12)1992 Foreigners 964 11.2 (108)

19951998 Foreigners 558 11.8 (66)2001 Foreigners 29 48.3 (14)c

2001 Party attendees 92 78.5 (55/70)19992002 Laboratory attendees 132 12.1 (16)2002 University employees 56 55.4 (31)2003 Foreigners 11 63.6 (7)2004 Recruits 77 31.2 (24)2005 Recruits 35 57.1 (20)c

onventional faecal examination.

d.e indiscriminate use of antibiotics effective against C.s and the lack of adequate diagnostic capability (Torres-t al., 2006). Greater awareness of the parasite in thesencreased familiarity with the disease it causes, alongved surveillance programmes for Cyclospora, increaselity that future outbreaks will be detected.

d sex distribution

loping countries, risk categories for cyclosporiasismunocompromised patients, foreigners and children.nown that the infection causes signicant morbidityity in immunodepressed individuals, in particular thosefection. The risk of faecal carriage and severity of ill-ated to the state of immunosuppression of the patients.atriates, the disease is common (Clarke and McIntyre,aggi et al., 1998; Shields and Olson, 2003; Puente et al.,e et al., 2006, 2007) and outbreaks have been reported

riasis has been found to be common in children. Mostes on prevalence of the infection and association withe been conducted in children that have attended clin-ls or laboratories and have been skewed towards thosel manifestations. The highest risk of infection and diar-in the rst ve years of life (Hoge et al., 1995; MadicoOrtega et al., 1998; Chacn-Bonilla et al., 2001; Bern etchildren less than 18 months of age, Cyclospora infec-Probable source of exposure References

UKb Shlim et al. (1991)Drinking water Rabold et al. (1994)Drinking water Hoge et al. (1993)

Fruits, vegetables Fryauff et al. (1999)UK Blans et al. (2005)

Watercress Ayala-Gaytn et al. (2004)UK Zini et al. (2004)Salads, juices Botero-Garces et al. (2006)Raspberry juice Puente et al. (2006)Vegetables sauces Torres-Slimming et al. (2006)Food, water Mundaca et al. (2008)

L. Chacn-Bonilla / Acta Tropica 115 (2010) 181193 187

tions were undetected in Nepal (Hoge et al., 1995), uncommon inGuatemala (Bern et al., 1999) and Venezuela (Chacn-Bonilla et al.,2001) and present but asymptomatic in Peru (Ortega et al., 1993).It is not known if it is due to weaning maternal antibodies or tolimited env

The comscarce. In athe coccidiuet al., 1997)al., 1998), th11 years. Induras (Kamal., 2003), Val., 2005) anfrequent inage distribudominantmby exposuryoung childcant differereported.

3.4. Season

In additthe prevaleeral endemregions andsonal trendof maximal(Kaminsky,1995; Shercsia (Fryauffincreases dnearly all threlated toGand early sShields andmore preva1999b) andcooler andductuationsity (Eberhaof cyclospo(Turgay et agests that ethis parasit

3.5. Reservo

The roleuncertain b

Effort tovitrohavebparasite in tet al., 2000)parasite andsis. Howevedescribed indogs and pSmith et al.al., 2001; Shium has bethe reportsC. cayetanen

Oocysts considered to be those of C. cayetanensis were observedin a duck from Peru (Zerpa et al., 1995), in the pooled faeces ofsome 600 young chicken from poultry farms and in pooled caecalcontents from another 50 from a market of Mexico (Garca-Lpez

996)hand2002and Eant

rasiteing ppigs,ora-er, iay dlospoet a

suggnensis we. Recin oner ths thral h

urce

ect pely bespoThuss caninat

nmencomm

biolagen th

riousies, fad ocert

Wateterboive dIn ato w

rinkings wt al.s useThreora13). Inrinatrbau

on w

sia,Nmixsold

s weipal wironmental exposure in this age group.munity based studies of Cyclospora age distribution are2-year cross sectional study in Peru, the prevalence ofm was highest among children aged 24 years (Madico. In this study and other from the same region (Ortega ete infectionwas not detected among persons older thanseveral studies fromGuatemala (Bern et al., 1999), Hon-insky, 2002), Hait (Lpez et al., 2003), Cuba (Nunez etenezuela (Chacn-Bonilla et al., 2007), Nepal (Kimura etd Turkey (Turgay et al., 2007) the infection was moreschool children

188 L. Chacn-Bonilla / Acta Tropica 115 (2010) 181193

isms were not completely removed (Rabold et al., 1994). In otherstudy, drinkingwater and sewagewaterwere identied as possiblesources of cyclosporiasis (Sherchand and Cross, 2001). In Vietnam,Cyclospora oocysts were identied in drinking water, rivers andlakes (Mieg

In Africafactors forwas an imdetected invehicle of tthe oocysts2005). In Alsources, incular recent cin this cityand of freshnance of thusing the sareas, at lea(Table 5).

These npotential towater, recrein endemicconsumed rthat waterbbut conclus

In theCyclospora dthose cause(Dawson,20was in Chicaply (Huangprotozoan dsis has beenThe presencimportance

3.6.2. FoodbIn thede

eating vege(Nimri, 200etables samagriculturalgreen leafyEgypt, the cand bivalvea study of trberries, buffactors for insuggest thafoods.Manyworldwide.been linkedPeru and In

Increasintravel and ato the spreareas. In thwhich havethoroughlycan inactivbeen showntured foods(Dawson, 2ous high-pr

contaminated raspberries inUSAandCanada (Herwaldt andAckers,1997; Herwaldt and Beach, 1999; Herwaldt, 2000; Ho et al., 2002;Shields and Olson, 2003; Dawson, 2005). Further outbreaks ofcyclosporiasis in USA, Canada and Europe were associated to the

ptiountrib;Heet aIn Uet aeat cheal

Soil tevelcycala

d thin dereadida, Uansce fransmer coiablee periminayo

he prern istrone po

s or sf thentactI 2.5thisora w(p