Services on Demand
Journal
Article
text in 
English (pdf)
Article in xml format
Article references
Automatic translation
Send this article by e-mailIndicators
-
Cited by SciELO -
Access statistics
Related links
-
Similars in
SciELO
Share
Permalink
Acta Médica Costarricense
On-line version ISSN 0001-6002Print version ISSN 0001-6012
Acta méd. costarric vol.54 n.3 San José Jul./Sep. 2012
Review
Key
aspects of coccidia associated with diarrhea in HIV patients
Authors’
Affiliation:
Abbreviations:
HIV: human
immunodeficiency virus, AIDS: acquired immunodeficiency syndrome
Correspondence:
luquesadalobo@hotmail.com
Abstract
Intestinal
parasites affect mainly developing
countries and constitute a public health problem, often related to the
lack of
efficient health systems, or drinking water sources. These are also
enhanced by
underlying diseases such as AIDS, which are also present in developed
countries. The literature describes that Cryptosporidium spp, Isospora
belli and Cyclosporacayetanensis are the parasites most
frequently
associated with persistent diarrhea in patients with advanced cases of
HIV/AIDS. This group of protozoa requires specific tests for diagnosis;
the
Ziehl-Neelsen stain is one of the non routine tests that allows
their identification. In most cases, it is not performed in the
laboratory if
not explicitly requested by the doctor.
Keywords: diarrhea,
coccidia, Cryptosporidium, Isospora, Cyclospora,
AIDS
Worldwide,
33,4 million people are infected with HIV;
most of them live in countries of low and middle income. It has been
estimated
that in 2010, 2,7 million people were infected.1 In late
stages of
the disease, there is a decrease in the number of CD4+ cells, below 200
cells/mm³ and development of opportunistic infections, tumors, and
neurologic complications.2
Tropical
intestinal parasitoses principally affect
developing countries and constitute a public health problem, often
related with
the lack of an efficient health system, sources of drinking water; but
also
accentuated by underlying diseases, like HIV, that also affect
developed
countries. The literature describes Cryptosporidium spp, Isospora
belli and
Cyclosporacayetanensis as the parasites most frequently
associated with
persistent diarrhea and weight loss, in patients with advanced cases of
HIV/AIDS.3-8
Likewise,
it has been described as one of the
parasites associated with diarrhea cases in children younger than 5
years of
age, with a prevalence that varies from 7,7%
up to
85,1%.3,4 The objective of this review is to highlight the
coccidia
that play a role as the main agents in episodes of diarrhea in patients
with
HIV/AIDS, the pathology in these patients and the diagnostic tools.
The
species of the genre Cystoisospora (Isospora) are
parasitic protozoa that belong in the Apicomplexaphylum, which
are also
known as coccidia. The term coccidia also
involves the species Cryptosporidium, Toxoplasma gondii and
other
members of the Eimeriorina suborder. In general terms, coccidia
are
characterized for having complex life cycles. However, members of the
genre Cystoisospora
are capable of completing their life cycle in a single host. The
oocysts of
the species in the Cystoisospora genre contain two sporocysts,
each one
with four sporozoites. The oocysts of the genre Toxoplasma and
Sarcocystis,
among others, are constituted in a similar way, but these parasites are
heteroxenous and have an intermediate vertebrate host, unlike Isospora,
which is the reason they belong in another family of coccidia.5
It is not
possible to determine if the authors in
early descriptions referred to C. belli or species of Sarcocystis.
An example of this confusion can be found in a pioneer work about coccidiosis
of E.R. Becker, published in 1934. Becker includes sketches that
exemplify
the sporulation of C. belli, but when referring to the
parasite, he does
as
Infections
by C. belli are cosmopolite, but
they appear with a higher frequency in tropical and subtropical
regions,
especially in Haiti, Mexico, Brasil, El Salvador, Africa, Middle East
and
Southeast Asia.6,7,8 During a
longitudinal
study conducted in Los Angeles with patients with HIV/AIDS, it was
determined
that the prevalence of C. belli found among 16.351 patients
through 8
years, was of 1%. This prevalence was higher when patients were born in
In another
research conducted in Port-au-Prince,
Haiti, 20 out of 131 (15%) patients with HIV/AIDS with opportunistic
infections
were infected with C. belli.9 In Sao Paulo, Brasil,
of 81
feces samples from immunocompetent patients, all of them resulted
negative for C.
belli; while, from other 81 samples of feces from patients with
HIV/AIDS,
13 resulted positive (9,9%).10 Among developed countries,
in Spain,
3 out of 60 samples (5%) of patients with HIV/AIDS with diarrhea were
positive
for oocysts of C. belli.11
Domestic
animals like the pig, the dog, the cat and
the rabbit, are not appropriate definite hosts to harbor the infection.12,13
Nonetheless, it is unknown if other animals could serve as hosts
during
transmission of C. belli, but the existence of paratenic hosts
could
explain why infections occur where sanitary measures are correct.5
C. belli produces,
in immunocompetent patients, an episode characterized by steatorrhea,
cephalea,
fever, malaise, abdominal pain, vomiting, dehydration and weight loss.
Blood in
stools is not a common finding, as the peripheral eosinophilia observed
in some
patients. The disease tends to chronicity, with parasites on feces or
in biopsy
samples, even months or years later, and recurrence is frequent.14,15,16
The
disease is more sever in children as compared to
adults. There is a record of a child 6 months old that remained with an
infection by C. belli for 30 weeks, which had a fatal outcome,
despite
the continuous parenteral nourishment.17 In this case, the
diarrhea
was characterized by stools of 1 to
In
individuals with other immunocompromises,
cystoisosporiasis also tends to be more severe in comparison with the
immunocompetent patient. There are cases reported of infections with C.
belli in patients with Hodgkin´s disease,14
with non-Hodgkin lymphoproliferative disease,19 in
adults with
T cell leukemia associated with type I human virus of T cells20 and
in patients with acute lymphoblastic leukemia.21
The
diarrhea due to an infection with C. belli in
individuals with AIDS is normally a secretory-type diarrhea, which,
besides the
febrile episode and the significant weight loss, leads to a very severe
dehydration that requires hospitalization. Despite these findings,
intestinal
lesions caused by C. belli and the response to the treatment
are similar
in immunosuppressed and immunocompetent patients.5
There have
been described cases of extraintestinal
cystoisosporiasis in patients with AIDS.22,23 This type of
episode
can be present as a history of dysphagia, nauseas, vomiting and profuse
diarrhea, with a significant weight loss and in association with
opportunistic
infections like Pneumocystis carinii, cytomegalovirus and
candidiasis.22
During autopsies it has been determined the presence of severe
cachexia,
erythematous and hemorrhagic foci in small intestine, ulcerations up to
The drug,
for both treatment and profilaxis, is the
trimethoprim-sulfamethoxazole (TMP-SMX). Ciprofloxacine is the
alternative in
those cases in which the TMP-SMX is contraindicated (hypersensitivity,
severe
hematological disorders, infants younger than 2 months old, among
others). In a
randomized controlled trial, 22 patients with AIDS and infection with C.
belli were assigned 160 and 800 mg of TMP-SMX, respectively or,
500 mg of
ciprofloxacine twice a day during 7 days.24 Those who
responded
clinically and microbiologically later received prophylaxis during 10
weeks
(one dose 3 days a week). The diarrheic episode was resolved in 10 of
12
patients treated with ciprofloxacine. Only one of the patients treated
with
TMP-SMX continued excreting Cystoisospora, even on day 7
post-treatment,
but without diarrheic symptoms, and with 3 additional days of
treatment, there
were no more oocysts detected in the feces. Another option is
pyrimethamine
associated with folic acid during 14 days, followed by prophylactic
doses.25
Tyzzer was
the first to establish the genre Cryptosporidium,
as well as to acknowledge the existence of various species through
studies with
C. muris from mice.26 After
the
discovery of Cryptosporidium, nearly 50 years passed during
which the
parasite was constantly confused with coccidia from the Sarcocystisgenre.
Such confusion between both genres was because many of the oocysts of Sarcocystisspp.have
a thin wall that frequently breaks and frees sporocysts, each one with
four
sporozoites, such as the oocysts of Cryptosporidium that
harbor in their
interior four sporozoites.27 In the last years, various
molecular
characterizations of Cryptosporidium have contributed to
elucidate the
confused taxonomy of this protozoan, as well as to validate the
existence of
multiple species. As a result there are C. andersoni in
cattle, C.
canis in dogs, C. felis in cats, C. hominis in
humans, C.
baileyi in chickens and other birds, C. galli in birds, C.
meleagridisin birds and humans, C. molnari in fish, C.
murisin
rodents and other mammals, C. parvum in ruminants and humans, C.
wrairi in guinea pigs, C. saurophilum and C. serpentis in
lizards
and snakes.26-32
The
infectious form of Cryptosporidium corresponds
to the oocyst, a resistance element of the parasite which permits the
dissemination of the infection. The oocyst presents a wall that can be
either
thin or thick, which is related with different ways of sporogonic
development
and infection.27
Most
recent efforts regarding research on
cryptosporidiosis are directed mainly towards the ecological
characterization
of the parasite, its infection sources, and the associated risk
factors. For
this purpose, resources have been used such as molecular instruments,
identification of metabolic pathways typical of Cryptosporidium for
the
development of therapeutic drugs, and the clarification of the immune
response
during the infection.33 Thanks to these efforts, the
complete
sequencing of the genome was made easier for Cryptosporidium
parvum,
Cryptosporidium hominis and Cryptosporidium muris.
Cryptosporidiosis
is an infection distributed
worldwide and it is among the most important emergent diarrheic
diseases of the
group of infections transmitted by contamination of food or water. Many
of the
cases are sporadic, but nearly 10% are epidemic-type episodes
originated by the
consumption of contaminated water and food.24
Cryptosporidiosis
is responsible of high morbidity and
mortality among patients infected with HIV. Within this group of
people, those
who have diarrhea elevate the prevalence up to 14% and 24% in developed
and
developing countries respectively.34
In a study
conducted with 275 patients with AIDS stage
disease and with chronic diarrhea, it was determined that the causal
agent in
15,6% of the cases was Cryptosporidium spp. Out of that group,
33,3%
were homosexual persons, and 10,6% used intravenous drugs. A 30% of the
15,6% infected patients with Cryptosporidium
spp., also
suffered of extraintestinal cryptosporidiosis.35
In 1982,
the Center for Disease Control in
Cryptosporidium
is most
studied of the coccidia associated with diarrhea; therefore,
it is the
one for which more information is available regarding its pathology and
immunology. It infects mainly the small intestine. Regardless of the
species,
infection with Cryptosporidium spp. manifests itself as a
diarrheic
episode in 90% of cases. The immunocompetent patient ends up
controlling the
infection; it is characterized as an aqueous diarrhea, acute and
self-limiting,
that lasts from 5 to 10 days. However, in patients with defects in
immune
cellular response (AIDS, malnutrition, leukemia, etc.), Cryptosporidium
frequently
causes a chronic diarrhea that could involve the biliary tract.41
Despite
numerous investigations on animal models
conducted with Cryptosporidium pavrum, the reach of these
models to
explain the human immunological response is limited. The clinical
perspective
in rodents is far from the human one, as the mice don’t develop
diarrhea
after the infection. Nonhuman primates; although they could probably be
the best
model, since they mimic the human disease; they present many technical
difficulties in comparison with the murine models. Cryptosporidium
hominis,
the principal causal agent of cryptosporidiosis, infects only human and
gnotobiotic pigs, these makes the animal models used for its study very
limited. To make the analysis even more difficult, the comparison that
emerges
between the animal and human models shows that the immunological
response is
very far from each other. For example, it looks like in the mouse, the
production of IFN is associated with innate and primary responses,42,43 while it is
possible that in
the human it is more associated with the memory response towards the
parasite.44
Cryptosporidium
spp. has
been detected in mesenteric lymphatic nodules.45It is
believed that
these are also sites that trigger an adaptive immune response. In the
infection
by Cryptosporidium, the secretion of chemokines by the
epithelial cells
produces recruitment of activated T cells towards the own lamella,
which come
from the Peyer plates, via NLM and through circulation. Regarding the
presence
of antibodies, even though there have been found specific immune
globulines
subtype IgG, IgM, IgA and IgE in patients infected and convalescent, it
has
been proven that mice with B cell depletion were able to resolve the
infection
by Cryptosporidium. At any rate, the secretory IgA would
collaborate in
controlling the infection, by blocking the entrance of the luminal
stages of
the parasite.45
During the
course of the infection the following are
produced: IL-8, chemokine ligand 5 (CCL5 or RANTES), monocyte
chemotactic
protein-1 (MCP-1) and macrophagic inflammatory protein-
Pulmonary
compromise is a rare complication of
intestinal cryptosporidiosis, it has been described in patients that
are
immunocompromised; most of them with advanced HIV/AIDS disease.
Clinical
manifestations of pulmonary cryptosporidiosis are unspecific and
include
chronic cough, fever and dyspnea as the most frequent symptoms, and it
can be
accompanied or not by radiologic signals.46
The
patient with immunocompetence often resolves the infection
by himself. In the immunocompromised patient, the severity of the
symptoms and
the development of the disease justify the use of therapeutic drugs. In
the
patient with AIDS, it is vital to reestablish, as far as possible,
immunity, by
means of highly active antiretroviral therapy, including HIV-protease
inhibitors.47
Regarding
an effective treatment, specific against Cryptosporidium
spp., there is no determined drug that yet exists in the market.24
Only the nitazoxanide, the paromomycin
and some macrolides
combined with other antibiotics, are considered moderately recommended,
without
them being considered curative. Nitazoxanide has been utilized in a
dose of
500-1500 mg twice a day, during several weeks, even months. Paromomycin
can be
used on immunocompetent patients at a dose of 1500-2000 mg daily,
during 7-14
days, to reduce symptoms, but without eradicating Cryptosporidium.
In
patients with AIDS, paromomycin appears to have no effect. Among the
macrolides, various trials catalog the spiramycin, the clarithromycin,
and the
azithromycin, as drugs with doubtful efficiency in patients with AIDS.
It is
possible that Rifabutin, administered as prophylaxis against Mycobacterium
aviaum, has a protective effect in a percentage of the cases of
patients with
AIDS.24
In 1986,
Soave and coworkers48 described a
diarrheic episode in four travelers returning from
When a
susceptible host consumes water or food
contaminated with infectious oocysts, the sporozoites are freed to
infect the
intestinal epithelium of the duodenum and jejunum. After two cycles of
asexual
replication, type I y II meronts are formed; and this last form
differentiates
in sexual forms or gametocytes. The macrogametocyte is fertilized by
the
microgametocyte and a zygote is produced, from which the oocyst
develops, it
will then be excreted through feces in the form of non-sporulated
oocysts.50
A great
part of the information regarding the
epidemiology of Cyclospora comes from tourists and countries
where the
protozoan is endemic, like
The
infection by Cyclosporais characterized by
anorexia, nausea, flatulence, fatigue, abdominal pain, diarrhea, low grade fever and weight loss.56-60 Clinical
presentation varies slightly between non-endemic and endemic areas,
where
asymptomatic infections are more frequent. The clinical symptoms are
more
severe in children. In the endemic regions, the episodes tend to be
more
favorable each time as the patient advances in his life and the
duration of the
infection is shorter. In the elderly, as in children, the symptoms
become more
severe again.53,56,61
Infection
by Cyclospora can be asymptomatic in
endemic regions and immunocompetent patients. However, severe diarrhea
has been
reported in both cases. There are a few reports of fatal outcomes in
cases of
infection by Cyclospora.62 In immunocompetent
patients a
moderate weight loss is experienced (
In both
immunocompetentand immunocompromised patients,
co-infections with Cyclospora, Cryptosporidium and other parasites have
been
described.69 Moreover, Cyclosporaoocysts have been detected
in
samples of non-gastrointestinal origins. There are two reports of the
presence
of oocysts in sputum of HIV-positive patients, with a background of
pulmonary
tuberculosis,70,71this suggests
that
Cyclosporacould be considered an opportunistic pathogen.
Treatment
with TMP-SMX, in various dosage schemes, has
resulted effective in most cases to cure the diarrhea and to achieve
the neutralization
in the feces samples. Ciprofloxacin is the second choice treatment. The
recurrence rate of this infection is higher when prophylactic treatment
is not
applied after treatment with the previously mentioned drugs.24
Diagnosis
Cystoisospora
belli, Cryptosporidium spp.
and Cyclosporacayetanensis can be detected in feces samples by
very
similar methods. In the three cases, the fixed and dyed samples with
Ziehl-Neelsen
or Kinyoun techniques allow the observation of the oocysts with a color
that
goes from light pink to an intense red. In the case of Cystoisospora
belli,
the identification of anoocystthat is usually non-sporulatedand of
20-30 um in
diameter, can also be done using the Giemsa stain and that produces
neon-blue
auto fluorescence, at a wave length of 330-380 nm.72 In
order to
detect Cryptosporidium spp. in feces and other fluids, like
sputum and
biliary contents, fluorescence techniques have been developed with the
use of
specific antibodies, as well as other molecular techniques; however,
acid-resistant stains continue to be the used commonly. The importance
of these
techniques is that, depending on their design, they help identify the
species
of Cryptosporidium, which is fundamental at an epidemiologic
level,
since there are anthroponotic and anthropozoonoticspecies.24
Conclusions
Allcoccidiosis
associated to diarrhea in
immunocompetent individuals are characterized by an acute diarrhea,
normally self-limited.
In immunocompromised patients, the disease can acquire severe forms,
potentially fatal. People affected by the acquired immunodeficiency
syndrome
are particularly prone to suffer severe forms of cryptosporidiosis.
In regard
to the approach for coccidiosis caused
by Cystoisospora belli and Cyclosporacayetanensis, it
does
possess an adequate treatment scheme, especially relevant in the
patient with
AIDS. Up to date, what appears to generate the best response for the
treatment
of diarrhea by Cryptosporidium, is
the
nitazoxanide; unfortunately, an antiparasitic that is 100% effective
against
this agent still does not exist.
Opportunistic
infections continue causing morbidity
and mortality in patients with HIV all over the world, and the CD4+
count is
strongly associated to the probability of progression of these diseases
and
death in these patients. Random and controlled trials and cohort
studies, have
documented that retroviral therapy reduces the incidence of
opportunistic
infections and, therefore, mortality.
It must be
remembered that this group of protozoa
require specific tests for its diagnostic. The intestinal coccidia can
be distinguished with the Ziehl-Neelsentinction, one of the
nonroutinary tests
that allow its identification and, that in many occasions, is not
performed
unless requested by the physician.
References
1. Oatway, James. Diez datos sobre el VIH/SIDA, Organización Mundial de
2. Fauci A, Pantaleo G, Stanley S. y Weissman D. Immunopathogenic mechanisms of HIV infection. Ann Intern Med. Apr 1996; 124: 654-663. [ Links ]
3. Kassi RR, Kouassi RA, Yavo W, Barro-Kiki CP, Bamba A, Menan HI, et al. Cryptosporidiosis and isosporiasis in children suffering from diarrhoea in
4. Schnack FJ, Fontana L, Barbosa PR, Silva LS, Baillargeon CM, Barichello T, et al. Enteropathogens associated with diarrheal disease in infants (< 5 years old) in a population sample in Greater Metropolitan Criciúma, Santa Catarina State, Brazil. Cad Saude Publica. 2003; 19:1205-1208). [ Links ]
5. Lindsay, D. et al., 1997, Biology of Isospora spp. from Humans, Nonhuman Primates, and Domestic Animals. Clinical Microbiology Reviews, 97: 19–34. [ Links ]
6. Faust, E. C., L. E. Giraldo, G. Giraldo, and R. Bonfante. 1961. Human occidiosis in the western hemisphere. Am. J. Trop. Med. Hyg. 10:343–350. [ Links ]
7. Junod, C., M. Nault, and M. Copet. 1988. La coccidiosis a Isospora belli chez es sujets immuno-competents. Bull. Soc. Pathol. Exot. 81:317–325. [ Links ]
8. Sorvillo, F. J., L. E. Lieb, J. Seidel, P. Kerndt, J. Turner, and L. R. Ash. 995. Epidemiology of isosporiasis among persons with acquired immunodeficiency syndrome in
9. DeHovitz, J. A., J. Pape, M. Boncy, and W. D. Johnson. 1986. Clinical manifestations and therapy of Isospora belli infection in patients with the acquired immunodeficiency syndrome. N. Engl. J. Med. 315:87–90. [ Links ]
10. Sauda, F. C., L. A. Zamarioli, W. E. Filho, and L. B. Mello. 1993. Prevalence of Cryptosporidium sp. and Isospora belli among AIDS patients attending
11. Ros, E., J. Fueyo, J. Llach, A. Moreno, and X. Latorre. 1987. Isospora belli infections in patients with AIDS in
12. Foner, A. 1939. An attempt to infect animals with Isospora belli. Trans. R. oc. Trop. Med. Hyg. 33:357–358. [ Links ]
13. Jeffery, G. M. 1956. Human coccidiosis in
14. Brandborg, L. L., S. B. Goldberg, and W. C. Breidenbach. 1970. Human coccidiosis—a possible cause of malabsorption: the life cycle in small-bowel mucosal biopsies as a diagnostic feature. N. Engl. J. Med. 283:1306–1313. [ Links ]
15. Henderson, H. E., G. W. Gillepsie, P. Kaplan, and M. Steber. 1963. The human Isospora. Am. J. Hyg. 78:302–309. [ Links ]
16. Jarpa Gana, A. 1966. Coccidiosis humana. Biológica (
17. Liebman, W. M., M. M. Thaler, A. DeLorimier, L. L. Brandborg, and J. Goodman. 1980. Intractable diarrhea of infancy due to intestinal coccidiosis. Gastroenterology 78:579–584. [ Links ]
18. Teschareon, S., P. Jariya, and C. Tipayadarapanich. 1983. Isospora belli infection as a cause of diarrhoea. Southeast Asian J. Trop. Med. Public Health 14:528–530. [ Links ]
19. Hallak, A.,
20. Greenberg, S. J., M. P. Davey, W. S. Zierdt, and T. A. Waldmann. 1988. Isospora belli infection in patients with human T-cell leukemia virus type I-associated adult T-cell leukemia. Am. J. Med. 85:435–438. [ Links ]
21. Westerman, E. L., and R. P. Christensen. 1979. Chronic C. belli infection treated with co-trimoxazole. Ann. Intern. Med. 91:413–414. [ Links ]
22. Michiels, J. F., P. Hofman, E. Bernard, M. C. St. Paul, C. Boissy, V. Mondain, Y. LeFichoux, and R. Loubiere. 1994. Intestinal and extraintestinal Isospora belli infection in an AIDS patient. Pathol. Res. Pract. 190:1089–1093. [ Links ]
23. Restrepo, C., A. M. Macher, and E. H. Radany. 1987. Disseminated extraintestinal isosporiasis in a patient with acquired immune deficiency syndrome. Am. J. Clin. Pathol. 87:536–542. [ Links ]
24. Derouin, F. y Lagrange-Xelot, M. 2008. Treatment of parasitic diarrea in HIV-infected patients. Expert Rev Anti Infect. Ther. 6(3) 337-249. [ Links ]
25. Weiss L. M., Perlman D. C.,Sherman J. y col.1988. Isospora belli infection:treatment with pirimetamina.Ann. Inter. Med.109:474-475. [ Links ]
26. Tyzzer, E.
27. Xiao, L., R. Fayer, U. Ryan, and S. J. Upton. 2004. Cryptosporidium taxonomy: recent advances and implications for public health. Clin. Microbiol. Rev. 17:72-97. [ Links ]
28. Alvarez-Pellitero, P., and A. Sitja-Bobadilla. 2002. Cryptosporidium molnari n. sp. (Apicomplexa: Cryptosporidiidae) infecting two marine fish species, Sparus aurata L. and Dicentrarchus labrax L. Int. J. Parasitol. 32:1007–1021. [ Links ]
29. Fayer, R., J. M. Trout, L. Xiao, U. M. Morgan, A. A. Lai, and J. P. Dubey. 2001. Cryptosporidium canis n. sp. from domestic dogs. J. Parasitol. 87:1415– 1422. [ Links ]
30. Lindsay, D. S., S. J. Upton, D. S. Owens, U. M. Morgan, J. R. Mead, and B. L. Blagburn. 2000.Cryptosporidium andersonin. sp. (Apicomplexa: Cryptosporiidae) from cattle,Bostaurus.J. Eukaryot.Microbiol.47:91–95. [ Links ]
31. Morgan-Ryan, U. M., A. Fall, L. A. Ward, N. Hijjawi,
32. Xiao, L., R. Fayer, U. Ryan, and S. J. Upton. 2004. Cryptosporidium taxonomy: recent advances and implications for public health. Clin. Microbiol. Rev. 17:72-97. [ Links ]
33. Lihua Xiao, 2009, Overview of Cryptosporidium Presentations at the 10th Internacional Workshops on Opportunistic Protists. [ Links ]
34. Dillingham RA, Lima AA, Guerrant RL. 2002. Cryptosporidiosis: epidemiology and impact. Microbes Infect. 4(10), 1059-1066. [ Links ]
35. Jokipii L, Pohjola S, Jokipii AM. Cryptosporidium: A frequent finding in patients with gastrointestinal symptoms. Lancet 1983; 2:358-361. [ Links ]
36. Human cryptosporidiosis--
37. Crawford FG, Vermund SH. Human cryptosporidiosis. Crit Rev Microbiol 1988; 16:113-159. [ Links ]
38. Melo CJA, Carvalho MI, Salgado MJ. An outbreak of cryptosporidiosis in a hospital day-care centre. Epidemiol Infect 1988; 101:355-359. [ Links ]
39.Nwanyanwu OC, Baird JN, and Reeve GR. Cryptosporidiosis in a day-care center. Tex Med 1989; 85:40-43. [ Links ]
40. Ravn P, Lundgren JD, Kjaeldgaard P, et al. Nosocomial outbreak of cryptosporidiosis in AIDS patients. Br Med J 1991; 302:277-80. [ Links ]
41. Hunter, P. R., and G. Nichols. 2002. Epidemiology and clinical features of Cryptosporidium infection in immunocompromised patients. Clin. Microbiol. Rev. 15:145–154. [ Links ]
42.
43. Lacroix, S., R. Mancassola, M. Naciri, and F. Laurent. 2001. Cryptosporidium parvum-specific mucosal immune response in C57BL/6 neonatal and gamma interferon-deficient mice: role of tumor necrosis factor alpha in protection. Infect. Immun. 69:1635–1642. [ Links ]
44. White, A. C., P. Robinson, P. C. Okhuysen, D. E. Lewis, I. Shahab, S. Lahoti, H. L. DuPont, and C. L. Chappell. 2000. Interferon gamma expression in jejunal biopsies in experimental human cryptosporidiosis correlates with prior sensitization and control of oocyst excretion. J. Infect. Dis. 181:701– 709. [ Links ]
45. Del Coco V. F., Córdoba M. A., Basualdo J. A.. 2009. Criptosporidiosis: una zoonosis emergente. Rev. argent. microbiol. vol.41, n.3, pp. 185-196. [ Links ]
46. Dupont C, Bougnoux ME, Turner L, Rouveix E, Dorra M. Microbiological findings about pulmonary cryptosporidiosis in two AIDS patients. J Clin Microbiol 1996; 34: 227-9. [ Links ]
47. Propio E., Morales MA. 2005. The impact of HIV-protease inhibitors on opportunistic parasites. Trends Parasitol. 21(2), 58-63. [ Links ]
48. Soave, R., J. P. Dubey, L. J. Ramos, and M. Tummings.
49. Ortega, Y. R., C. R. Sterling, R. H. Gilman, V. A. Cama, and F. Diaz. 1993. Cyclospora species—a new protozoan pathogen of humans. N. Engl. J. Med. 328:1308–1312. [ Links ]
50. Ortega, Y. R., R. H. Gilman, and C. R. Sterling.
51. Albert, M. J.,
52. Alfano-Sobsey, E. M., M. L. Eberhard, J. R. Seed, D. J. Weber, K. Y. Won, E. K. Nace, and C. L. Moe. 2004. Human challenge pilot study with Cyclospora cayetanensis. Emerg. Infect. Dis. 10:726–728. [ Links ]
53. Behera, B., B. R. Mirdha, G. K. Makharia, S. Bhatnagar, S. Dattagupta, and J. C. Samantaray. 2008. Parasites in patients with malabsorption syndrome: a clinical study in children and adults. Dig. Dis. Sci. 53:672–679. [ Links ]
54. Pratdesaba, R. A., M. Gonzalez, E. Piedrasanta, C. Merida, K. Contreras, C. Vela, F. Culajay, L. Flores, and O. Torres. 2001. Cyclospora cayetanensis in three populations at risk in
55. Caryn Bern Michael J. Arrowood Mark Eberhard James H. Maguire, Cyclospora in
56. Connor, B. A., J. Reidy, and R. Soave. 1999. Cyclosporiasis: clinical and histopathologic correlates. Clin. Infect. Dis. 28:1216–1222. [ Links ]
57. Fleming, C. A., D. Caron, J. E. Gunn, and M. A. Barry.
58. Herwaldt, B. L., and M. L. Ackers. 1997. An outbreak in 1996 of cyclosporiasis associated with imported raspberries. The Cyclospora Working Group. N. Engl. J. Med. 336:1548–1556. [ Links ]
59. Ortega, Y. R., R. Nagle, R. H.Gilman, J.Watanabe, J. Miyagui, H. Quispe, P. Kanagusuku, C. Roxas, and C. R. Sterling.1997.Pathologic and clinical findings in patients with cyclosporiasis and a description of intracellular parasite life-cycle stages.J.Infect.Dis.176:1584–1589. [ Links ]
60. Shlim, D. R., M. T. Cohen, M. Eaton, R. Rajah, E. G. Long, and B. L. Ungar. 1991. An alga-like organism associated with an outbreak of prolonged diarrhea among foreigners in
61. Bendall, R. P., S. Lucas, A. Moody, G. Tovey, and P. L. Chiodini. 1993. Diarrhoea associated with cyanobacterium-like bodies: a new coccidian enteritis of man. Lancet 341:590–592. [ Links ]
62. Burrell, C., S. Reddy, G. Haywood, and R. Cunningham. 2007. Cardiac arrest associated with febrile illness due to
63. Shields, J. M., and B. H. Olson. 2003. PCR-restriction fragment length polymorphism method for detection of Cyclospora cayetanensis in environmental waters without microscopic confirmation. Appl. Environ. Microbiol. 69:4662–4669. [ Links ]
64. Shlim, D. R., M. T. Cohen, M. Eaton, R. Rajah, E. G. Long, and B. L. Ungar. 1991. An alga-like organism associated with an outbreak of prolonged diarrhea among foreigners in
65. Sancak, B., Y. Akyon, and S. Erguven. 2006.Cyclospora infection in five immunocompetent patients in a Turkish university hospital. J. Med. Microbiol. 55:459–462. [ Links ]
66. Sifuentes-Osornio, J., G. Porras-Cortes, R. P. Bendall, F. Morales-Villarreal, G. Reyes-Teran, and G. M. Ruiz-Palacios. 1995. Cyclospora cayetanensis infection in patients with and without AIDS: biliary disease as another clinical manifestation. Clin. Infect. Dis. 21:1092–1097. [ Links ]
67. Connor, B. A., D. R. Shlim, J. V. Scholes, J. L. Rayburn, J. Reidy, and R. Rajah. 1993. Pathologic changes in the small bowel in nine patients with diarrhea associated with a coccidia-like body. Ann. Intern. Med. 119: 377– 382. [ Links ]
68. Zar, F. A., E. El-Bayoumi, and M. M. Yungbluth. 2001. Histologic proof of acalculous cholecystitis due to Cyclospora cayetanensis. Clin. Infect. Dis. 33:E140–E141. [ Links ]
69. Bellagra, N., F. Ajana, C. Coignard, M. Caillaux, and Y. Mouton. 1998. Co-infection with Cryptosporidium sp. and Cyclospora sp. in an AIDS stage HIV patient. Ann. Biol. Clin. (
70. Di Gliullo, A. B., M. S. Cribari, A. J. Bava, J. S. Cicconetti, and R. Collazos. 2000. Cyclospora cayetanensis in sputum and stool samples. Rev. Inst. Med. Trop. Sao Paulo 42:115–117. [ Links ]
71. Hussein, E. M., A. H. Abdul-Manaem, and S. L. el-Attary. 2005. Cyclospora cayetanensis oocysts in sputum of a patient with active pulmonary tuberculosis, case report in
72.
