Retr ospective study of the occur r ence of Cyclospora cayetan en sis
at Clinical Hospital of the Univer sity
of São Paulo Medical School, SP
Estudo retrospectivo da ocorrência de
Cyclo spo ra ca yeta nensis
no Hospital das Clínicas da Faculdade de Medicina
da Universidade de São Paulo, SP
Elenice Messias do Nascimento Gonçalves
1, Iaiko Horroiva Uemura
1, Vera Lúcia Pagliusi
Castilho
1and Carlos Eduardo Pereira Corbett
2ABSTRACT
Cyc lo spo r a c ayetanensis c a u se s wa te ry di a rrhe ai n tro pi c a l c o u n tri e s, a m o n g tra ve le rs a n d a f te r i n ge sti o n o f c o n ta m i n a te d wa te r a n d f o o d . Ve ry li ttle i s k n o wn a b o u t i ts e p i d e m i o lo gy, p a th o ge n i c a sp e c ts a n d re se rvo i rs. In Bra zi l, i ts p re va le n c e i s u n k n o wn a n d to d a te th e re h a ve b e e n re p o rts o f th re e o u tb re a k s. We re p o rt h e re a re tro sp e c ti ve stu d y o f 5 ,0 1 5 sto o l sa m p le s f ro m 4 ,8 6 9 p a ti e n ts a tte n d e d a t Cli n i c a l Ho sp i ta l o f th e Un i ve rsi ty o f Sã o Pa u lo Me d i c a l Sc h o o l, SP, Bra zi l b e twe e n Ap ri l 1 9 9 6 a n d Ja n u a ry 2 0 0 2 , wi th 1 4 c a se s o f Cyc lo spo r a c aye tane nsis b e i n g d e te c te d th e re wa s a p re va le n c e o f 0 .3 %. Of th e 1 4 i n f e c te d p a ti e n ts, th e m e a n a ge wa s 3 8 ye a rs a n d 7 1 .4 % we re f e m a le . Te n p a ti e n ts p re se n te d sym p to m s; si x p re se n te d le ve ls o f i m m u n o lo gi c a l m a rk e rs a n d f i ve p a ti e n ts we re i m m u n o d e f i c i e n t.
Ke y-words: Cyc lo spo r a c aye tane nsis. Pre va le n c e . Cyc lo sp o ri a si s. Pa ra si to lo gy. Pa th o lo gy. Bra zi l.
RESUMO
Cyc lo spo r a c aye tane nsis c a u sa d i a rré i a lí q u i d a e m p a í se s tro p i c a i s, vi a ja n te s e a p ó s i n ge stã o d e á gu a e a li m e n to s c o n ta m i n a d o s. Mu i to p o u c o é c o n h e c i d o so b re su a e p i d e m i o lo gi a , a sp e c to s p a to gê n i c o s e re se rva tó ri o s. No Bra si l, su a p re va lê n c i a é d e sc o n h e c i d a c o m re la to d e trê s su rto s. Nó s re la ta m o s u m e stu d o re tro sp e c ti vo d e 5 .0 1 5 a m o stra s f e c a i s p ro ve n i e n te s d e 4 .8 6 9 p a c i e n te s a te n d i d o s n o Ho sp i ta l d a s Clí n i c a s d a Fa c u ld a d e d e Me d i c i n a d a Un i ve rsi d a d e d e Sã o Pa u lo , SP, Bra si l e n tre a b ri l d e 1 9 9 6 e ja n e i ro d e 2 0 0 2 c o m d e te c ç ã o d e 1 4 c a so s d e c i c lo sp o rí a se e p re va lê n c i a d e 0 ,3 %. De ste to ta l 7 1 ,4 % e ra m d o se x o f e m i n i n o c o m i d a d e m é d i a d e 3 8 a n o s. De z a p re se n ta ra m si n to m a to lo gi a , se i s ti n h a m n í ve i s d e m a rc a d o re s i m u n o ló gi c o s e c i n c o i m u n o d e f i c i ê n c i a .
Pal avr as-chave s: Cyc lo spo r a c aye tane nsis. Pre va lê n c i a . Ci c lo sp o rí a se . Pa ra si to lo gi a . Pa to lo gi a . Bra si l.
1 . Ce ntr al Lab o r ato r y Divisio n. Clinic al Ho spital. Unive r sity o f São Paulo Me dic al Sc ho o l, São Paulo , SP. 2 . Lab o r ato r y o f Me dic al Inve stigatio n in Infe c tio us Dise ase Patho lo gy. Unive r sity o f São Paulo Me dic al Sc ho o l, São Paulo , SP.
Suppo r te d b y DLC – HCFMUSP, LIM 0 3 , LIM 5 0 & CNPq . Addr e ss to: Dr. Car lo s Eduar do Pe r e ir a Co r b e tt. De pto
de Pato lo gia/FM/USP. Av. Dr. Ar naldo 4 5 5 /1 º andar, sala 1 2 1 5 , 0 1 2 4 6 - 9 0 3 São Paulo , SP, B r asil. Te le fax: 5 5 1 1 3 0 8 1 -7 7 9 9
e -mail: c c o r b e tt@ usp. b r
Re c e b ido par a pub lic aç ão e m 4 /2 /2 0 0 4 Ac e ito e m 8 /5 /2 0 0 5
Cyclo spo ra ca ye ta ne nsis is an emerging and opportunistic c oc c idium, first desc ribed as a c ausal agent of human infec tion in 1 9 7 94; it was inc luded in the Cyclo spo ra genus in 1 9 9 32 0 with referenc ed spec ies in 1 9 9 41 9. To date, 1 7 spec ies of Cyclo spo ra have been identified through the use of molec ular methods, although humans are the only host of Cyclo spo ra ca ye ta ne nsis and no animal model has been identified9 2 7. The exac t means of transmission are still unknown; but it is probably by fec al-oral route, through the ingestion of sporulated ooc ysts, whic h are
1 0
µ
m in stool smears stained by Kinyoun´s modified method, also used for the detec tion of other c oc c idian parasites. It is nec essary to measure these ooc ysts through a mic rometer, sinc e Cyclo spo ra ca ye ta ne nsis ooc ysts c an be easily seen in phase c o n tr a s t a n d fluo r e s c e n c e m ic r o s c o pe s1 2 1 9 2 0 2 9. Oo c ys t sporulation in 2 .5 % potassium dic hromate c an also be used2 9. Cyc losporiasis has been reported in many c ountries, but it seems to be more c ommon in tropic al and subtropic al regions2 7 2 8. Its prevalenc e in Brazil is still unknown, with a c ase reported in Rio de Janeiro ( RJ)2 4, a c ase in B rasilia ( DF)3, 1 0 c ases in the State of Goiás ( GO)1 3 1 4, 3 c ases in Juiz de Fora ( MG)6 and a c ase in São Paulo ( SP)1 0. Three outbreaks have been registered: two in General Salgado ( SP) , one in November 2 0 0 0 and another in January 2 0 0 1 , and the third in Antonina ( PR) , in November 2 0 0 11 1 2 5 2 7. The objec tive was to perform a retrospec tive study of 5 ,0 1 5 stool samples, c ollec ted from 4 ,8 6 9 patients attended at Clinic al Hospital of the University of São Paulo Medic al Sc hool ( HC-FMUSP) between April 1 9 9 6 and January 2 0 0 2 , with 1 4 detec ted c ases of Cyclo spo ra ca ye ta ne nsis.MATERIAL AND METHODS
Clinical Hospital of the University of São Paulo Medical School ( HCFMUSP) , located in São Paulo, Brazil. This is a highly specialized public hospital, associated to the University of Sao Paulo with 3 ,2 7 1 beds and 9 ,8 8 8 employees and attends patients referred from the Public Health System and a small number of private patients as well as those with healthcare insurance. The Parasitology Service of the Division of the Central Laboratory of HC-FMUSP performs a monthly average of 1 0 ,0 0 0 parasitologic tests.
A retrospec tive study of 5 ,0 1 5 stool samples derived from 4 ,8 6 9 patients was c onduc ted. The samples were sent to our Servic e for Cyclo spo ra ca ye ta ne nsis investigation, from April 1 9 9 6 to January 2 0 0 2 . All samples were submitted to standard c onc entration methods: Hoffman, Pons and Janer, Faust and c ols and modified Rugai method; they were stained with an iodine solution for the diagnosis of helminthes and protozoa ( PPF) . For the identific ation of Cyclo spo raca ye ta ne nsis, the Kinyoun´s modified method1 2 was used in all samples, followed by oocyst sporulation in 2 .5 % potassium dichromate, whenever samples were positive. All oocysts were measured through an ocular micrometer. Samples were considered positive for Cyclo spo ra ca ye ta ne nsis when they presented spherical structures that stained in different shades of red, or colorless, with size varying from 8 -1 0
µ
m.Statistical analysis. For the positive results, data suc h as age, sex, symptoms, diseases and immunologic al markers were c ollec ted from the hospital rec ords using MS Offic e Exc el version 2 0 0 0 . In order to c harac terize positive samples for Cyclo spo ra ca ye ta ne nsis, we present the relative and absolute frequenc ies of eac h qualitative variable. Regarding the quantitative variables, means and medians wer e used to summar ize the data and sta nda r d e r r o r s, sta nda r d de via tio ns, a nd m inim um a nd maximum value s we r e use d to indic ate data var iab ility. To de te r m ine r isk fa c to r s fo r Cyc lo sp o ra c a ye ta n e n si s, we c o mpar e d the po sitive patie nts with 6 0 r ando mly se le c te d
patients, from the general population, with no infec tion. For the qualitative variables such as sex, diarrhea, disease and symptoms, we c ompared the frequenc y distribution between the positive and negative groups through Pearson’s Chi-square test3 1. Fisher’s exac t test was used in situations where the expec ted values were lower than 5 . For p values lower than 0 .0 5 , we c onsidered the assoc iation among the variables to be statistic ally signific ant. To c ompare the groups regarding the quantitative variables suc h as age, CD3 , CD4 , CD8 and CD4 /CD8 ratio, we applied Student’s t-test3 1, in o rder to c o mpare the means o f the independent populations. For p values lower than 0 .0 5 , we c onsidered that the two groups are different regarding patients’ age.
RESULTS
Spheric al organisms with a mean diameter of 9
µ
m, showing an internal granular struc ture and great ac id-alc ohol resistant staining variability were identified in 1 4 stool samples, diagnosed as Cyclo spo raca ye ta ne nsis ( Figure 1 ) and listed as follows: 1 . MKG, 2 3 -year-old single male, born and residing in São Paulo,artisan. He denied using tobac c o, alc ohol and illic it drugs. Patient was HIV-positive, homosexual, in a stable relationship. He lived with his parents. He came to the hospital complaining of persistent diarrhea for the previous 4 months, with 3 to 4 bowel movements a day. The patient had lost 1 7 kg in 5 months. In April 1 9 9 6 , his CD4 c ount was 1 0 4 T-c ells/
µ
l and his stool sample was submitted to c onc entration and staining methods, whic h resulted positive for Cyc lo spo ra c a ye ta ne nsis.2 . ASM, 4 2 -year-old married female, residing in São Paulo and an employee at the Division of Nutrition and Dietetic s of HC-FMUSP, during a routine parasitologic test in July 1 9 9 7 she presented a diagnosis for the presenc e of Cyclo spo ra ca ye ta ne nsis in her stool sample. She had no symptoms or assoc iated diseases.
3 . RCS, 3 8 - ye a r- o ld s in gle m a le , r e s idin g in Sã o Pa ulo , homosexual. He was attended at the Extended Care Center for the HIV/AIDS patient, with AIDS symptoms and diarrhea, in September 1 9 9 7 . His sto o l sample was sub m itte d to
c onc entration and staining methods, and was positive for Cyclo spo raca ye ta ne nsis; his CD4 T c ell c ount was 1 6 2 /
µ
l. 4 . LCS, 4 7 -year-old widower, born in the State of B ahia and residing in São Paulo, with AIDS; she was attended at the Extended Care Center for the HIV/AIDS patient. In July 1 9 9 9 , she presented anorexia, loss of 2 0 kg of body weight in a 3 -month period, fever ac c ompanied by produc tive c ough with yellowish sputum, bloody-muc ous diarrhea for a period of one year, with an average of ten bowel movements a day and swallowing diffic ulty. Her skin was dry and pale. CD4 T-c ell c ount was 8 4 c ells/µ
l; her stool sample was submitted to c o nc e ntr atio n and staining me tho ds, and was po sitive fo r En ta m o e b a c o li , En ta m o e b a h i sto lyti c a / d i sp a r, Schisto so m a m a nso ni and Cyclo spo ra ca ye ta ne nsis. 5 . LFNS, 5 0 -year-old single male, homosexual, born in Rio deJaneiro, has been residing in São Paulo for 2 2 years. The patient was a smoker, but denied using illic it drugs. Patient had AIDS and c ame to the hospital for management of the dise ase , pr e se nting go o d ge ne r al he alth status and no gastrointestinal alterations. His CD4 T c ell c ount was 1 2 6 c ells/
µ
l, and his stool sample was submitted to c onc entration and staining metho ds, and was po sitive fo r Cyc lo spo ra c a ye ta ne nsis.6 . MSS, 5 7 -year-old married female, born and residing in São Paulo. She denied using tobac c o, alc ohol or illic it drugs. In August 1 9 9 9 she c ame to the hospital ER c omplaining of headac he, nausea, and vomiting. She reported a loss of 2 kg in a 3 -week period and bloody diarrhea for 2 0 days. Her CD4 T c ell c ount was 7 3 c ells/
µ
l, and her stool sample test was positive for Cyclo spo raca ye ta ne nsis.7 . TAS, 2 4 -year-old, single female, born in the State of Bahia and residing in São Paulo for 3 months. She reported sinusitis, b r o n c h i e c ta s i a a n d h yp o ga m m a gl o b u l i n e m i a s i n c e c hildhood. She presented c hronic diarrhea, with an average of 3 bowel movements a day. She c ame to the hospital for a clinical investigation at the Immunology Service. In September 2 0 0 0 , her CD4 T c ell c ount was 2 9 5 c ells/
µ
l and her stool sample tested positive for Cyclo spo ra ca ye ta ne nsis. 8 . LFC, 5 3 -year-old married female, residing in Goiânia, State ofGoiás. She underwent a laboratory investigation as a probable bone marrow donor in October 2 0 0 0 , with no diseases or symptoms. Laboratory tests were positive for hepatitis C and the parasitologic analysis of the stool revealed the presence of Cyclo spo raca ye ta ne nsis. She did not return to the Service. 9 . ET, 4 0 -year-old female, born and residing in General Salgado,
São Paulo. She presented persistent diarrhea, with an average of 1 0 bowel movements a day. Her stool sample was submitted to labo rato ry investigatio n fo r the presenc e o f pro bable etiologic agent, whic h was the c ause of the diarrhea that affec ted inhabitants of that town in November 2 0 0 0 . The parasitologic analysis performed through c onc entration and staining methods was positive for Cyclo spo raca ye ta ne nsis. 1 0 . OM, 3 0 -year-old male, born and residing in General Salgado, SP. He presented persistent diarrhea, with an average of 1 0 bowel movements a day. His stool sample was submitted to
laboratory investigation for the presence of probable etiologic agent, whic h was the c ause of the diarrhea that affec ted inhabitants of that town in November 2 0 0 0 . The parasito lo gic analysis thr o ugh c o nc e ntr atio n and staining me tho ds was po sitive fo r Cyc lo sp o ra c a ye ta n e n si s.
1 1 . MJCL, 4 0 -year-old, married female, born and residing in São Paulo. The patient had hepatitis C and sc hizophrenia, with no gastrointestinal symptoms. She c ame to the hospital for routine management, and presented good general health status in January 2 0 0 1 . The parasitologic analysis was positive for Cyclo spo raca ye ta ne nsis.
1 2 . ESS, 1 9 -year-old, single female, born and residing in São Paulo. The patient had had Hodgkin’s disease for 7 years. She denied tobac c o, alc ohol and illic it drug use. In February 2 0 0 1 , she c ame to ho spital ER with fever, vo miting and diarrhea for a period of 3 days, with an average of 5 bowel movements a day. The stool sample analysis was positive for Cyclo spo ra ca ye ta ne nsis.
1 3 . SGV, 2 0 -year-old, single female, born and residing in São Paulo. She denied tobac c o, alc ohol and illic it drug use. The patient had sic kle-c ell anemia. In May 2 0 0 1 she c ame to the hospital for a c linic al investigation at the Hematology Servic e, presenting nausea, vomiting, abdominal pain and sporadic diarrhea. The parasitologic analysis through c onc entration a n d s ta i n i n g m e th o ds wa s p o s i ti ve fo r Cyc lo s p o r a c a ye ta ne nsis.
1 4 . MJA, 5 3 -year-old, married female, born and residing in São Paulo. In May 2 0 0 1 she came to the hospital and was attended at the Gastroenterology Servic e of HCFMUSP, for a c linic al investigatio n o f c hr o nic c o nstipatio n. The sto o l sample a n a lys is wa s po s itive fo r Bla s to c ys ti s h o m i n i s a n d Cyclo spo raca ye ta ne nsis. She did not return to the Servic e.
Statistical analysis. The oc c urrenc e in this population was 0 .3 % ( 1 4 /4 8 6 9 ) . Of the 1 4 infec ted patients, ten ( 7 1 .4 % ) were females and 4 ( 2 8 .6 % ) were males. Age varied from 1 9 to 5 7 years with a mean age of 3 8 years. Ten ( 7 1 .4 % ) patients presented symptoms, with diarrhea being the most frequent ( 9 0 % ) followed by vomiting ( 4 0 % ) , weight loss ( 3 0 % ) , nausea ( 2 0 % ) , fever ( 1 0 % ) , abdo minal pain ( 1 0 % ) and headac he ( 1 0 % ) . Six ( 4 2 . 9 % ) patie nts did no t pr e se nt e stab lishe d diseases and 5 ( 3 5 .7 % ) presented immunodefic ienc y, with 4 o f th e s e h a vin g AI DS a n d o n e h ypo ga m m a glo b ulin e m ia . Re gar ding the le ve ls o f im m uno lo gic al m ar k e r s, o nly six patients presented these registers, as shown in Table 1 .
Whe n an infe r e ntial analysis was pe r fo r me d in o r de r to determine the risk fac to rs fo r Cyc lo spo ra c a ye ta n e n sis, using
Table 1 - Descriptive statistics of levels of immu n ological markers.
Immunological no
Mean Median Standard Standard Minimum Maximum Marker Error Deviation
CD3 6 8 7 2 .3 9 3 2 2 0 8 .5 8 5 1 0 .9 1 3 0 4 1 5 1 6
CD4 6 1 4 0 .7 1 1 5 3 3 .4 8 82 73 2 9 5
CD8 6 6 7 0 .5 6 4 3 1 9 6 .5 6 4 8 1 .4 7 1 9 0 1 2 6 8
the c o ntr o l gr o up ( N = 6 0 ) and the po sitive gr o up ( N = 1 4 ) , we did no t o b se r ve any statistic ally signific ant asso c iatio n b e twe e n th e pr e s e n c e o f diffe r e n t s ym pto m s ( p> 0 . 0 5 ) , diar r he a ( p> 0 .0 5 ) , AIDS ( p> 0 .0 5 ) , and the asso c iatio n o f o the r par asite s ( p> 0 .0 5 ) ( Tab le s 2 , 3 , 4 and 5 ) .
Table 2 - Resu lts of the association regardin g presen ce of symptoms.
Kinyoun
negative positive Total
Presence of symptom no n 22 4 26
% 3 6 .7 2 8 .6 3 5 .1
yes n 38 10 48
% 6 3 .3 7 1 .4 6 4 .9
Total n 60 14 74
% 1 0 0 .0 1 0 0 .0 1 0 0 .0
p value = 0 .7 5 8 ( Fisher’s exact test)
Table 3 - Resu lts of the association regardin g the presen ce of diarrhea.
Kinyoun
negative positive Total
Diarrhea no n 30 5 35
% 5 0 .0 3 5 .7 4 7 .3
yes n 30 9 39
% 5 0 .0 6 4 .3 5 2 .7
Total n 60 14 74
% 1 0 0 .0 1 0 0 .0 1 0 0 .0
p value = 0 .3 3 5 ( Chi-square test)
Table 4 - Resu lts of the association regardin g AIDS.
Kinyoun
negative positive Total
AIDS no n 33 10 43
% 5 5 .0 7 1 .4 5 8 .1
yes n 27 4 31
% 4 5 .0 2 8 .6 4 1 .9
Total n 60 14 74
% 1 0 0 .0 1 0 0 .0 1 0 0 .0
p value = 0 .2 6 2 ( Chi-square test)
Table 5 - Resu lts of the association regardin g PPF.
Kinyoun
negative positive Total
PFP no n 45 12 57
% 7 5 .0 8 5 .7 7 7 .0
yes n 15 2 17
% 2 5 .0 1 4 .3 2 3 .0
Total n 60 14 74
% 1 0 0 .0 1 0 0 .0 1 0 0 .0
p value = 0 .4 9 9 ( Fisher’s exact test)
Re gar ding se x, Chi-sq uar e te st r e sults did no t pr e se nt statistic ally signific ant values at the usual level of 5 % ( p = 0 .0 5 8 ) b ut this te st sho we d a slight c o nc e ntr atio n o f fe male s ( 7 1 % ) in the infe c te d gr o up in c o mpar iso n to 4 3 .3 % in the he althy gr o up, as sho wn in Tab le 6 and Figur e 2 .
In relation to the quantitative variables: age, CD3 , CD4 , CD8 and CD4/CD8 ratio, we applied Student’s T-test and observed a statistically significant difference regarding CD4 only ( p< 0 .0 0 1 ) , with a mean of 1 4 1 cells/
µ
l, as depicted in the Table 7 and Figure 3 .Table 6 - Resu lts of the association regardin g sex.
Cyclo spo ra ca yeta nensis
negative positive Total
Sex female n 26 10 36
% 4 3 .3 7 1 .4 4 8 .6
male n 34 4 38
% 5 6 .7 2 8 .6 5 1 .4
Total n 60 14 74
% 1 0 0 .0 1 0 0 .0 1 0 0 .0
p value = 0 .0 5 8 ( Chi-square test)
Sex
Male Female
% 80
60
40
20
0
Kinyoun
Negative
Positive 29
71
57
43
Fi gu r e 2 - Co n ce n tr a ti o n s o f p o si ti ve a n d n e ga ti ve r e su l ts f o r Cyclo spo r a ca ye ta ne nsis, accor di n g to se x .
Table 7 - Results of the comparison of means for the quantitative variables.
Kinyoun N Mean SD p-value ( T-test)
Age negativo 60 3 0 .6 3 1 5 .2 7 0 .0 8 8
positive 1 4 3 8 .2 9 1 3 .0 9
CD3 negative 27 1 6 0 7 .9 9 8 9 .9 0 0 .0 8 9
positive 6 8 7 2 .3 3 5 1 0 .9 1
CD4 negative 27 4 4 2 .9 3 3 6 4 .4 4 < 0 .0 0 1 *
positive 6 1 4 0 .6 7 8 2 .0 0
CD8 negative 27 1 0 5 1 .4 7 9 0 .1 9 0 .1 5 1
positive 6 6 7 0 .5 0 4 8 1 .4 7
CD4 /CD8 negative 27 0 .6 0 4 0 .6 3 0 0 .1 7 5
positive 6 0 .3 4 6 0 .3 2 8
* statistically significant
6 27
N =
Kinyoun positive Negative
95 % CI CD 4
700,0
600,0
500,0
400,0
300,0
200,0
100,0
0,0
DISCUSSION
The occurrence of 0 .3 % ( 1 4 /4 8 6 9 ) in the studied population was considered low in comparison to the percentages found in Guatemala5, Peru1 3, Venezuela7, Haiti2 1, Nepal15, Egypt18, and Lagos1. A slight concentration of females ( 7 1 %) in the infected group in comparison to the healthy group is compatible with reports for North America2.
When Student’s t-test was applied3 1 fo r the c o mpar iso n between the means of the levels of immunologic al markers, we observed that CD4 , with a mean of 1 4 1 c ells/
µ
l, was statistic ally signific ant ( p< 0 .0 0 1 ) , showing that the c linic al manifestations c an b e asso c iate d with the ho st’s immuno lo gic al mar k e r s, similarly to c ryptosporidiosis1 6 2 8.When the study was analyzed regarding age range, presenc e o f sympto ms and/o r asso c iated diseases with the pr esenc e o f Cyc lo spo ra c a ye ta n e n si s, we o b se r ve d that the c linic al symptomatology in immunodepressed and immunoc ompetent patients, regardless of age, is not different from that c aused by Crypto spo ridium sp1 2 0 2 1, with diarrhea present in 6 4 .3 % and 5 0 % of the infec ted and c ontrol groups, respec tively, and did no t sho w a statistic ally signific ant asso c iatio n ( p> 0 . 0 5 ) , emphasizing the importanc e of the c linic al and laboratory results for the differential diagnosis of suc h parasites and c onsidering the treatments desc ribed for c yc losporiasis2 1 2 9 3 0.
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